Amadavad, India
A Study of Brentuximab Vedotin With Doxorubicin, Vinblastine and Dacarbazine in Adults With Hodgkin Lymphoma in India
Phase
4Span
83 weeksSponsor
TakedaNew Delhi
Recruiting
A Study to Evaluate the Effect of Fecal Transplant and Dietary Changes on Disease Activity in Patients With Newly Diagnosed Active Ulcerative Colitis
This study is a multi-center, double-blind, 2 × 2 factorial, randomized sham-controlled trial designed to evaluate the effects of fecal microbiota transplantation (FMT) and dietary modification in treatment-naïve patients with mild to moderate active ulcerative colitis (UC). The trial consists of four treatment arms: FMT + Anti-inflammatory Diet (AID) + 5-ASA (Group A) FMT + Sham Diet + 5-ASA (Group B) Sham Transplantation + AID + 5-ASA (Group C) Sham Transplantation + Sham Diet + 5-ASA (Group D) All groups receive 5-aminosalicylic acid (5-ASA) as the standard medical therapy. Study Setting The trial is conducted at six FMT centers across India, with one additional center dedicated to microbiome analysis: AIIMS, New Delhi, India Dayanand Medical College, Ludhiana, India PGIMER, Chandigarh, India Lisie Hospital, Kochi, India IMS, BHU, Varanasi, India Lokmanya Tilak Municipal Medical College, Mumbai, India IIIT-Delhi, India (for microbiome analysis) Intervention Details Fecal Microbiota Transplantation (FMT) Patients receive three FMT sessions (weeks 0, 2, 6) during induction and additional 8-weekly maintenance sessions (weeks 10, 18, 26, 34, 42) for responders. FMT is delivered via colonoscopy; at week 0, it is instilled into the right colon/terminal ileum (post bowel preparation), while for maintenance sessions, it is instilled in the left colon without bowel preparation. Each FMT dose is 50 g stool, freshly prepared within 4 hours of collection. Multiple donors are used to ensure microbiome diversity Anti-Inflammatory Diet (AID) Patients assigned to AID receive a nutritionally tailored diet that promotes T-regulatory cell expansion, microbiome stability, and gut barrier integrity. The diet excludes gluten-based grains, dairy products, and pro-inflammatory foods while including fermented foods, cruciferous vegetables, and polyphenols. Patients are provided diet charts, receive dietary counseling, and are monitored via diet app named IBDNutricare. Sham Interventions Sham FMT: Instead of donor stool, patients receive sterile water infusions via colonoscopy at the same time points as FMT. Sham Diet: Patients receive dietary counselling without specific modifications Randomization and Blinding Central randomization is conducted via REDCap. Block randomization will be done in which blocks of 8 will be created for the randomization. Further, stratified randomization will also be done in which <25% Proctitis involving Ulcerative Colitis patients. Blinding: Patients, investigators collecting clinical data, and those assessing endoscopic images are blinded. The endoscopist administering FMT and the dietitian providing dietary counseling are unblinded Data Collection and Assessments Baseline Assessments (Week 0) Clinical Evaluation: Patient-reported outcomes (PRO-2), stool frequency, rectal bleeding assessments. Laboratory Tests: Hemogram, renal/liver function, CRP, ESR, fecal calprotectin, and microbiome profiling. Endoscopy: Mayo Endoscopic Score (MES) assessment with high-definition recordings. Histology: Biopsy samples assessed using Robarts Histologic Index (RHI) and Distribution Chronicity and Activity (DCA) score Follow-up Assessments Week 10 (Induction phase endpoint): Endoscopy, histology, laboratory tests. Week 48 (Maintenance phase endpoint): Same assessments as baseline. Microbiome Analysis: Fecal samples collected at baseline, 10 weeks, and 48 weeks for metagenomics and metabolomics Safety Monitoring Adverse events graded using CTCAE criteria (Grade 1-5). Serious adverse events (SAEs) include hospitalization, disability, or life-threatening conditions Data Management Data is collected using paper Case Report Forms (CRF's) and then data will be entered in REDCap. Endoscopic images and videos are securely stored and centrally reviewed.
Phase
N/ASpan
157 weeksSponsor
All India Institute of Medical Sciences, New DelhiNew Delhi, Delhi
Recruiting
A Study to Evaluate the Effect of Fecal Transplant and Dietary Changes on Disease Activity in Patients With Newly Diagnosed Active Crohn Disease
This study is a multi-center, double-blind, factorial randomized controlled trial designed to evaluate the efficacy of microbiome manipulation strategies using fecal microbiota transplantation (FMT), Crohn's Disease Exclusion Diet (CDED), or their combination in treatment-naïve patients with mild to moderate active Crohn's Disease (CD). Study Setting The trial is conducted at six FMT centers across India, with one additional center dedicated to microbiome analysis: AIIMS, New Delhi, India Dayanand Medical College, Ludhiana, India PGIMER, Chandigarh, India Lisie Hospital, Kochi, India IMS, BHU, Varanasi, India Sion Hospital, Mumbai, India IIIT-Delhi, India(for microbiome analysis) Intervention Details: Fecal Microbiota Transplantation (FMT)- Patients receive a 3-day course of oral vancomycin (500 mg BD) before the first FMT. Freshly prepared 50 g stool is used for each FMT, and the transplant is administered within 4 hours of preparation. FMT is delivered via colonoscopy at weeks 0, 2, and 6, followed by 8-weekly maintenance sessions for responders at weeks 10, 18, 26, 34, 42. Multiple donors (n≥2) are used to ensure microbiome diversity. The first FMT session is instilled in the right colon/terminal ileum post bowel preparation, whereas maintenance sessions involve left-colon infusion without bowel preparation. Crohn's Disease Exclusion Diet (CDED)- Patients assigned to CDED follow a phased dietary protocol designed to limit exposure to pro-inflammatory dietary components and enhance gut microbiome stability. CDED consists of an induction and maintenance phase, with structured dietary charts and counseling provided by a dietitian. Compliance is monitored via telephonic interviews and a dedicated diet tracking app (IBD NutriCare). Sham Interventions- Sham FMT: Patients receive sterile water or saline infusions via colonoscopy at the same time points as FMT. Sham Diet: Patients receive general dietary advice but do not follow the CDED protocol. Randomization and Blinding- Central randomization is conducted using a secure web-based system (REDCap), utilizing stratified randomization based on disease extent. The study follows a double-blind approach: Blinded: Patients, clinical assessors, and endoscopic scorers. Unblinded: Endoscopists administering FMT/sham FMT and dietitians providing dietary counseling. Oral vancomycin and placebo capsules are identically packed to maintain blinding. Data Collection and Assessments- Baseline Assessments (Week 0) Clinical Assessment: Crohn's Disease Activity Index (CDAI), symptom scoring, and dietary adherence evaluation. Laboratory Tests: Hemogram, renal/liver function, CRP, ESR, fecal calprotectin, and microbiome profiling. Endoscopy: SES-CD scoring with high-definition endoscopic video recording. Histology: Biopsy samples are analyzed using Distribution Chronicity and Activity (DCA) scoring. Follow-up Assessments- Clinical assessments at weeks 0, 2, 4, 6, 10, and every 8 weeks thereafter. Endoscopic assessments at baseline, week 10, and week 48, with central reading of all videos. Fecal microbiome analysis at baseline, week 10, and week 48. Safety and Monitoring- Adverse Events (AEs) graded per CTCAE criteria (Grades 1-5). Serious Adverse Events (SAEs) include hospitalization, life-threatening conditions, or death. DSMB reviews interim safety data at week 10 and 24. Emergency unblinding is permitted for critical medical decisions. Data Management- Data is collected using REDCap, with role-based access controls. Endoscopic images and videos are securely stored for centralized analysis. Microbiome sequencing data is processed at IIIT-Delhi. Statistical Considerations- Sample size calculation: 168 patients (42 per arm, 90% power). Analysis Plan: Intention-to-treat (ITT) and per-protocol (PP) analyses. Longitudinal mixed-effects modeling for microbiome shift
Phase
N/ASpan
157 weeksSponsor
All India Institute of Medical Sciences, New DelhiNew Delhi, Delhi
Recruiting
A Study to Evaluate the Effect of Fecal Transplant and Dietary Changes on Disease Activity in Patients With Crohn Disease on Advanced Therapies
This is a multicenter, double-blind, factorial randomized controlled trial (RCT) evaluating the efficacy of microbiome manipulation strategies in patients with active Crohn's Disease (CD) undergoing advanced therapy (biologics or small molecules). The study will be conducted across six clinical centers in India, with an additional center designated for microbiome analysis. Randomization and Blinding: Randomization: Centralized, computer-generated randomization using permuted blocks of 8, 12, and 16 to ensure equal distribution across intervention arms. Stratification: Not more than 1/3rd patients should be biological therapy exposed Blinding: The blinded team includes patients and principal investigators. Endoscopists administering FMT/sham FMT and dietitians providing dietary counseling will be unblinded Sham-Control Methods: FMT Sham: Sterile clean water infusions via colonoscopy. Diet Sham: Dietary counseling without any modification Intervention Arms: Patients are randomized into one of four treatment groups: FMT + CDED + Advanced Therapy (Group A) FMT + Sham Diet + Advanced Therapy (Group B) Sham FMT + CDED + Advanced Therapy (Group C) Sham FMT + Sham Diet + Advanced Therapy (Group D) Fecal Microbiota Transplantation (FMT): FMT Route: Administered via colonoscopy. FMT Schedule: Induction Phase: Weeks 0, 2, and 6. Maintenance Phase: Every 8 weeks (weeks 10, 18, 26, 34, 42) for responders. Preparation: Donor Selection: Multi-donor approach with prescreening FMT Processing: 50 g stool freshly prepared and instilled within 4 hours. Delivery Locations: Week 0 (Bowel Preparation): Right colon/terminal ileum. Weeks 2 and 6 (No Bowel Preparation): Left colon. Crohn's Disease Exclusion Diet (CDED) Diet Structure: Induction Phase (Weeks 0-6): Elimination of specific pro-inflammatory dietary components. Maintenance Phase (Weeks 6-48): Gradual reintroduction of certain food groups. Monitoring: Adherence tracked using the IBD NutriCare app, diet recall logs, and DietCal software. Sham Diet: Patients follow a standard healthy diet with general dietary counseling. Assessments and Data Collection Baseline Assessments (Week 0) Clinical Data: Crohn's Disease Activity Index (CDAI), stool frequency, rectal bleeding, and symptom tracking. Laboratory Tests: Hemogram, renal/liver function tests, blood glucose. Inflammatory Markers: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fecal calprotectin (FCP). Microbiome Analysis: Stool samples stored at -80°C for sequencing. Endoscopic Evaluation: Scoring: Simple Endoscopic Score for CD (SES-CD). Blinded Central Review: Videos assessed by two independent readers; discrepancies adjudicated by a third reader. Histology: Biopsies analyzed using DCA score (Distribution Chronicity and Activity). Follow-up Assessments Visit Schedule: Induction Phase: Weeks 2, 4, 6, and 10. Maintenance Phase: Every 8 weeks (weeks 18, 26, 34, 42, and 48). Clinical Assessments: CDAI, PRO2 symptom tracking, medication adherence checks. Endoscopy: Week 10 and Week 48; central scoring of videos. Diet Adherence: Assessed at weeks 2, 4, 6, and 10, then every 8 weeks. Microbiome Sampling: Stool samples collected at weeks 10 and 48. Safety Monitoring and Adverse Events Adverse Event (AE) Classification: CTCAE Grading (Grade 1-5) for treatment-related AEs. Serious Adverse Events (SAEs): Hospitalization, life-threatening events, or disability. Safety Monitoring Plan: Pre-procedural safety checks for each FMT session. Immediate post-FMT monitoring (48 hours). Late safety assessments (14 days post-FMT, then every visit). Unblinding Procedure: Allowed only for SAE management with DSMB approval. Data Management and Statistical Analysis Electronic Data Capture (EDC): Platform: REDCap database with tiered access permissions. Audit Trails: Secure logs of data entry and modification. Dietary Data Processing: IBD NutriCare app logs converted into macronutrient composition reports. Adherence scoring based on 80% compliance threshold. Microbiome Data Processing: Samples sequenced at IIIT-Delhi, analyzed for diversity indices and metabolic pathways. Statistical Plan: Primary Analysis: Intention-to-treat (ITT) and per-protocol (PP) analyses. Longitudinal Modeling: Mixed-effects models for repeated measures. Effect Size Estimation: Sample size: 168 patients (42 per arm).
Phase
N/ASpan
157 weeksSponsor
All India Institute of Medical Sciences, New DelhiNew Delhi, Delhi
Recruiting
A Study to Evaluate the Effect of Fecal Transplant and Dietary Changes on Disease Activity in Patients With Ulcerative Colitis on Advanced Therapies
This study is a multicenter, randomized, factorial-design, double-blind, controlled trial investigating the effects of fecal microbiota transplantation (FMT) and dietary interventions in patients with mild to moderate, treatment-naïve, active inflammatory bowel disease. The trial is being conducted across multiple clinical centers, with a central microbiome analysis facility. Randomization and Blinding: Randomization: Centralized, computerized randomization is employed to ensure balanced treatment allocation. The permuted block method, along with stratification based on disease characteristics, ensures equal distribution across intervention arms Blinding: Patients, investigators collecting clinical data, and endoscopic video assessors are blinded to treatment allocation. The dietitian and endoscopist performing FMT (or sham FMT) are unblinded Intervention Arms: Participants are assigned to one of four treatment arms: FMT + Anti-inflammatory Diet (AID) +Advanced therapy FMT + Sham Diet+ Advanced therapy Sham FMT + AID+ Advanced therapy Sham FMT + Sham Diet+ Advanced therapy FMT is administered via colonoscopy at 0, 2, and 6 weeks, with responders receiving maintenance doses every 8 weeks until week 48 Participant Timeline and Assessments: Baseline Assessments: Clinical, laboratory, and endoscopic evaluations, including serological tests, inflammatory markers, and microbiome profiling. Follow-up Schedule: Visits occur at Week 0, Week 6, Week 10, and then every 8 weeks until Week 48. Endoscopic Monitoring: Colonoscopy is performed at baseline, Week 10, and Week 48. Centralized endoscopic video scoring ensures consistency Data Collection and Management: Paper CRF's and Electronic Data: The paper based CRF's will be filled first and then data will be entered into a REDCap software. Dietary Monitoring: Participants will use the IBD NutriCare mobile application for diet tracking. Microbiome Analysis: Fecal samples are processed and analyzed at a designated microbiome research center. Safety Monitoring and Compliance: Adverse Event Reporting: All safety events, including potential serious adverse events (SAEs), are logged and monitored by the Data and Safety Monitoring Board (DSMB). Protocol Deviations: Documented and assessed for impact on trial integrity. Training and Quality Control: Regular site training ensures adherence to the protocol, and periodic audits maintain data quality
Phase
N/ASpan
157 weeksSponsor
All India Institute of Medical Sciences, New DelhiNew Delhi, Delhi
Recruiting
Effect of Perioperative Oral Rifaximin on Early Graft Dysfunction in Adult Living Donor Liver Transplant
Methodology: - Study population: All patients undergoing adult living donor liver transplant recipients - Study design: Open label Randomized control Study - Study period: After ethical board clearance, all LDLT recipients satisfying inclusion criteria till June 2025 - Sample size: n=100 - Intervention: Preoperative Rifaximin supplementation 550 mg twice daily from preoperatively 2 weeks to post op POD 1 to 7 - Monitoring and assessment: Not valid - Adverse effects: No adverse effect is expected to occur out of study protocols. except vomiting, headache, dizziness, nausea - Stopping rule Not valid (b) Expected outcome of the project: Perioperative oral rifaximin decreases early allograft dysfunction in recipients of adult living donor liver transplant. (c) Ethical issues in the study and plans to address these issues: None expected
Phase
N/ASpan
57 weeksSponsor
Institute of Liver and Biliary Sciences, IndiaNew Delhi, Delhi
Recruiting
Effect of Laser Photobiomodulation in Improving Mouth Opening in Oral Submucous Fibrosis
Study design: A patient and outcome assessor blinded, multiple- arm, randomized, placebo controlled clinical trial Setting: All India Institute of Medical sciences New Delhi Selection of patients: Consecutive patients diagnosed with Oral Submucous Fibrosis based on WHO clinical criteria (Warnakulsurya et al 2007, 2021) and classified as Moderate Oral Submucous Fibrosis based on functional staging of More et al 2011 (Functional staging M2 and M3: maximal interincisal distance 15-35 mm) will be prospectively recruited after ethical clearance and informed written consent. Clinicopathologic characteristics: The clinical demographics, Tobacco and Areca nut habit history ( Type, quantity, frequency, duration), association with other habits like smoking/ smokeless tobacco with/ without slaked lime, alcohol and addictive drugs will be recorded. The clinical characteristics and staging/grading of OSMF would be recorded as per prepared proforma and protocol. The clinical grading of moderate OSMF will be done according to WHO clinical criteria and More et al 2011 classification. Biopsy of any suspicious oral lesions if found will be done to rule out malignancy and referred to the cancer center for further management and excluded from study. Enrolment of subjects fulfilling the inclusion and none of the exclusion criteria will be done after information and written informed consent before any further investigation. Routine blood investigations to rule out common systemic conditions ( CBC, Blood glucose, LFT, KFT) Participants will be randomized into three arms (1:1:1) Group A: Photobiomodulation therapy (parameters defined below) given intraorally on bilateral buccal mucosa and extraorally (sham) with conventional non-invasive management. Group B: Photobiomodulation therapy (parameters defined below) given intraorally (bilateral buccal mucosa) and extraorally (bilateral masseter muscle) with conventional non-invasive management. Group C: Sham (Use of laser handpiece with only red guide light and without using the foot pedal which activates the laser)Photobiomodulation therapy(Placebo) (Intraoral and Extraoral) with conventional non-invasive management. Randomization: Block randomization with varying block size will be done using computer generated random numbers using the Nquery software. Allocation concealment: Participants will be randomized using sequentially numbered, opaque sealed envelopes (SNOSE). 315 white envelopes will be prepared with aluminum foil sheet and carbon sheet in each. Assigned treatment protocol will be mentioned clearly on a paper and put in each envelope. For each treatment protocol 105 envelopes will be prepared and sealed. Each envelope will have an identifier of trial on its front. Envelopes will be opened sequentially by an operator blinded to the study protocol after which patients will be allotted a study arm as per the treatment mentioned in the envelope. Before opening the envelope we will write the patient's study identifier number, date and operator's signature in front of the envelope, which will be transferred on white paper through carbon paper. Used envelopes will be stored separately until the completion of trial. Blinding: The subjects will be blinded to the group assignment as they will receive PBM ( Active or Sham as per group assignment ) both intraorally and extraorally The outcome assessor will be blinded to the group assignment of the subjects as they will be identified by unique randomization code only Conventional non-invasive management (Usual care): All subjects in the three groups will receive the same standard conventional non- invasive management advised for moderate OSMF as per current scientific evidence. Brief behavioral Tobacco, areca nut and alcohol habit cessation counseling as per WHO 5As and 5Rs technique at baseline and each follow up. Oral prophylaxis Removal of oral irritational factors like sharp teeth, appliances or prosthesis, impacted buccoverted third molars, parafunctional habits Oral hygiene maintenance instructions Oral physiotherapy(Mouth opening and cheek ballooning exercises) Control of systemic conditions (Anemia, Diabetes, hypertension, thyroid disorders) by specialist referral Removal of all predisposing factors for oral candida infection Advocacy for safe sexual practices Nutrition and diet counseling( seasonal and regional food rich in nutrients, vitamins, antioxidants avoidance of spicy /sour/ hot foods and drinks) Regular surveillance for malignant transformation Photobiomodulation Therapy (PBM therapy): PBM will be given with 940nm long infrared wavelength diode laser with following specifications Biolase Epic X Diode LASER (USFDA and CE approved) LASER Classification- IV Medium- InGaAsP Semi-Conductor Diode Wavelength- 940+10nm Maximum Output Power= 10W Pulse repetition rate= upto 20kHz Pulse duration Rate= 0.01ms- 20ms Power modes- Continuous/ Pulsed Protocol for PhotoBioModulation( PBM) therapy Protocol for PBM therapy has been made as per guidelines of the consensus statement ( Zelcha et al 2016) regarding the applications, protocols, safety, dosimetric considerations of PBM in management of side effects of chemoradiation therapy in Head and neck cancers like mucositis and fibrosis. Protective laser wavelength specific eyewear will be used for patient, operator. The device will be used according to the manufacturer's instructions and calibration before each therapy in the trial. The surgical handpiece (diameter 0.6cm) will be used without the fibre optic tips in defocused mode and head sanitized before therapy. Peak Power : 0.3Watts Power density: 1 Watt/cm2 Fluence: 4J/cm2 per cycle Spot size : 0.28cm2 Distance : 2mm from surface Mode: Continuous, Non- contact mode, circular motion, overlapping, in clockwise concentric manner with laser handpiece perpendicular to surface Duration of cycle : 20 seconds with interval of 30 seconds alternating with other side Cycles per sitting: Three for each side Four Sittings: Day 0,3, 7, and 15 Intraoral: Bilateral buccal mucosa will be divided arbitrarily into three zones superior, middle and inferior for equal distribution of laser energy during each cycle Extraoral :Bilateral masseter muscle will be divided into three zones superior, middle and inferior for equal distribution of laser energy during each cycle Therapeutic monitoring: Site of application of LASER will be evaluated continuously for any discomfort, signs of inflammation like redness of skin/ mucosa during therapy and during follow up. The following options will be considered during therapy Move the Handpiece relative to the affected anatomy. Defocus the energy by moving the Handpiece further away from the skin. Decrease the power setting.(considering the Fitzpatrick Skin type scale) Stop/ Defer the treatment. Patient will be interviewed to know any adverse effects they might be feeling after initiation of treatment with Laser. Training of operators: All the operators giving intraoral and extraoral PBM therapy will be trained in the protocol as per study before subject recruitment. Withdrawal criteria: If any patient withdraws consent after treatment is initiated or develops any of the conditions mentioned in exclusion criteria, the patient will be withdrawn from the study. Protocol Deviation : When/If subjects develop changes suspicious of malignancy (erosion, ulceration, induration, exophytic growth) during follow up after Usual care/PBM, they will undergo incisional biopsy to rule out malignant changes and managed as per institutional protocol for oral malignant lesions by referral to cancer center at IRCH. Statistical Analysis: Data will be entered in an electronic data form and managed using Research Electronic Data Capture (REDcap) software. Comparison of baseline continuous variables will be compared between the two groups( A and C, B and C) using Unpaired T-test and categorical variables will be compared using Chi Squared Test or Fisher's Exact Test. The primary outcome measure- Interincisal Distance at maximum mouth opening will be compared between the two groups using Unpaired T-test and analyzed using Intention to Treat and Per Protocol Analysis. Secondary continuous outcome variables will be compared between the two groups using Unpaired T-test or Wilcoxon Rank Test as appropriate. Secondary categorical outcome variables will be compared between the two groups for two proportions/Z-test. Comparison between primary and secondary outcome variables between groups A and B will also be done using the same scheme although the sample size is not estimated for the same. Results will be presented as Difference in Means/Proportions with 95% confidence interval and p<0.05 will be considered statistically significant.
Phase
N/ASpan
174 weeksSponsor
Dr. Shalini GuptaNew Delhi, Delhi
Recruiting
Healthy Volunteers
FMT for Alcohol Use Disorder in Cirrhotics.
Hypothesis :- - FMT is useful in reducing craving and return to heavy drinking in patients with alcohol related cirrhosis with active drinking, through modulation of gut microbiota and correction of dysbiosis Aim and Objective - - To assess the efficacy of FMT in decreasing lapse, relapses and maintaining alcohol abstinence in AUD in patients with cirrhosis Study population: - Patients with cirrhosis with recent alcohol use attending outpatient clinic at ILBS, New Delhi Study design: - Open label, parallel group, randomized, controlled study. Study period: - 1 year Sample size with justification: - Assuming that abstinence in Placebo group is 50% and we assume that there will be 40% absolute increase in FMT group (90%; Bajaj JS, Hepatology 2021) with alpha 5 and power of 80%, investigator need to enroll 48 cases, further assuming 10 % dropout rate it was decided to enroll 54 cases that is 27 in each group.
Phase
N/ASpan
49 weeksSponsor
Institute of Liver and Biliary Sciences, IndiaNew Delhi, Delhi
Recruiting
New Delhi, Delhi
Recruiting
Cortical Excitability in West Syndrome Using Transcranial Magnetic Stimulation
PATIENT ENROLLMENT AND MANAGEMENT: - Consecutive children with West Syndrome (clinical spasm with EEG correlate) will be screened in the study centre for eligibility, and after applying inclusion and exclusion criteria they will be worked up for etiology. - History will be taken and clinical examination will be done and if either are suggestive of any underlying etiology specific investigations will be performed as indicated (Ex. Neurocutaneous markers in tuberous sclerosis). - If there are no other etiological pointers available from history and examination or if there is any history suggestive of adverse perinatal events, MRI brain with epilepsy protocol will be done. - If MRI is not suggestive of structural etiology, they will be given a vitamin trial (pyridoxine 30mg/kg/day, pyridoxal phosphate- 20mg/kg/day, biotin 10mg/day and folinic acid 15mg/day) for a period of 10 days for response. Those who respond to vitamin trial will be excluded from the study. - Written informed consent will be taken from legal guardians who are willing to participate in the study. Their anti-epileptic drugs will be optimized. Inappropriate AEDs like phenytoin, phenobarbitone and carbamazepine will be discontinued and replaced with valproate/levetiracetam and clonazepam in adequate doses and will be made in tablet form. - DASII will be administered by child psychologist and will be repeated at 6 months of follow-up wherever feasible. ACTH therapy - Appropriate screening for Tuberculosis as per unit protocol (Mantoux and CXR screening) will be done if going to receive ACTH therapy. - Children fulfilling the inclusion and exclusion criteria, will be enrolled and started on high dose regimen of 150 U/m2 or 6 U/kg of ACTH. - This high dose will be continued for 2 weeks following which they will be slowly tapered over remaining 4 weeks, for a total treatment duration of 6 weeks. - RBS and BP monitoring to be done twice weekly. - EEG and TMS parameters will be done at baseline, 6 weeks and 3 months of therapy. - First follow-up will be at 6 weeks of treatment initiation, then at 8 weeks and from then on once a month for a minimum period of 3 months (+/- 7 days) upto 6 months (+/- 7 days) wherever feasible. - Those who have had complete electroclinical spasm cessation will be continued of oral AEDs. - The overall spasm reduction will be calculated from the mean number of spasms from the observation period week and the mean number of spasms from the 6th week of therapy. Adverse effects will be noted down in their seizure diary. - For sustained electroclinical cessation those who had complete electroclinical response will be rechecked at the end of 3 months (+/- 7 days) upto 6 months (+/- 7 days) wherever feasible. - Compliance rate, adverse events, >50% spasm reduction rate, clinical spasm cessation rate, complete electroclinical spasm cessation rate will also be calculated from patient seizure log and EEG correlate. - After 3 months, those who have >/=50% spasm reduction rate will be given trial of other oral AEDs as per protocol. - But those who have <50% spasm reduction rate will be given an option to choose between ketogenic diet and vigabatrin. KD therapy - Children who have <50% spasm reduction rate, and opt for ketogenic diet, will be explained and counselled regarding the process of initiation and maintenance of dietary therapy. - A window period of 5 to 7 days will be given for the pre-initiation of KD workup which includes ECG, RFT, LFT, CBC, Lipid profile, Urine calcium creatinine ratio and USG KUB for nephrocalcinosis. - Children will be admitted in ward and initiated on Ketogenic diet under supervision. - KD will be initiated in a ratio of 2:1 and then hiked to 2.5:1 in the next day and subsequently to 3: on day 3. Urine ketones will be checked daily using ketone dipsticks. - For better assurance of ketosis and tolerance the indigenous KD will be supplemented with readymade formula for the initial period of 4 weeks after starting KD and then shifted to complete indigenous KD gradually over 1 week. - If ketosis is not achieved by day 5 of starting KD, the ratio will be hiked to a maximum of 4:1 from day 6. - Patient will be discharged as soon as the desired ratio of KD is achieved, and the parents are adequately motivated and confident. Telephonic contacts will be made in regular intervals to further ensure compliance at home. - Those children who are unable to tolerate taking adequate ketogenic diet therapy requiring discontinuation of therapy, will be considered as deviates. - The overall spasm reduction will be calculated from the mean number of spasms from the observation period week and the mean number of spasms from the 6th week of KD therapy. - Failure of KD: Children with response rate if not >50% spasm reduction by 6 weeks or no electroclinical cessation of spasm by 3 months, will be considered to have failed KD and shifted to standard anti-seizure medications as per protocol. - KD will be continued if there is more than 50% spasm reduction. - EEG and TMS will be done at 6 weeks and 3 months of KD therapy in case of clinical spasm cessation and wherever clinically indicated. - First follow-up will be at 6 weeks of KD treatment initiation, 8 weeks and then once monthly for a minimum period of 3 months and 6 months wherever feasible. For sustained electroclinical cessation those who had complete electroclinical response will be rechecked at the end of 3 months (+/- 7 days) upto 6 months (+/- 7 days) wherever feasible. - Compliance rate, adverse events, >50% spasm reduction rate, clinical spasm cessation rate, complete electroclinical spasm cessation rate will also be calculated from patient seizure log and EEG correlate. - Formula based KD would be supplied to the patient free of cost. But the company will play no part in the study design, conduct, data collection or analysis. TMS Intervention Protocol: PARAMETERS METHODS Resting Motor Threshold (MT) - Single pulse TMS Site of stimulation - Motor Cortex Coil type- Circular coil MCF-125 (Coil outer diameter: 121 mm; Transducer head: 140.5 x 41.5 mm) Hemisphere - Bilateral hemisphere EMG recording - Contralateral APB muscle Short interval cortical inhibition (SICI) - Paired pulse TMS in dominant hemisphere ISI - 3 msec Conditioning pulse - 80% of MT Test stimulus - 120% of MT Long interval cortical inhibition (SICI) - Paired pulse TMS in dominant hemisphere ISI - 100 msec Conditioning pulse - 120% of MT Test stimulus - 120% of MT Total Time Duration - 30 min The TMS will be given by machine make Magventure model no X100 with Magoption made in Denmark with standard circular coil as mentioned above. Data Management and Analysis Data recording would be done in a Microsoft Excel spreadsheet (Microsoft Office, Microsoft Corp., Seattle, WA, USA). Descriptive: Mean/Median/Range/Standard Deviation/Frequencies would be used to describe the demographic profile of participants and their comorbidities Comparative: A comparison between the two groups would be done. Categorical variables would be compared using Chi square/ Fischer's exact test. Depending upon the distribution of continuous variables - - Student "t" test would be used for parametric variables. - Mann Whitney U test would be used for nonparametric variables. Differences with p value of 0.05 or lower will be considered significant. Ethical aspects Ethical clearance: The study will be conducted after obtaining Ethical clearance from the Institute Ethical Committee. Essentiality and Justification for the study: This study would be beneficial in generating a hypothesis as an initial step bringing new insights into seizure pathogenesis, planning individualized antiepileptic drug therapy and studying treatment response. Consent: Patients will be enrolled only after obtaining informed written consent from the parents/guardians. Privacy and confidentiality: Confidentiality of the records will be maintained. The parents/guardians will have full authority to enroll or withdraw the child from the study and this will not affect the future care and treatment given to the child in our hospital. Costs of the investigations and therapy Investigations such as EEG and TMS whenever required will be done at no additional cost. Immunotherapy which is the standard of care will be provided to the patient. All children included in the study would be examined in detail and the investigations and standard of care would be advised after they have fulfilled the inclusion criteria. Since, the investigators would be following the standard of care in every child, hence, every child enrolled would be benefitted. The side effects and details of the investigations and intervention shall be explained to the parents in the language they understand the best and consent will be taken accordingly.
Phase
2/3Span
122 weeksSponsor
All India Institute of Medical Sciences, New DelhiNew Delhi, Delhi
Recruiting