Assessment of Psilocybin (TRP-8802) in Concert With Psychotherapy in Patients With Irritable Bowel Syndrome (IBS)

Phase

Condition

Colic

Gastrointestinal Diseases And Disorders

Lactose Intolerance

Treatment

Psychotherapy

TRYP-0082

Clinical Study ID

NCT06206265

TRYP-003

Ages 21-64
All Genders

Study Summary

Participants with IBS (all subtypes) and with no exclusionary comorbid psychiatric or medical disorders will be enrolled in the study.

This study will involve a randomized waitlist control design to investigate the rapid and sustained effects of TRP-8802 following two experimental sessions in which an oral dose of TRP-8802 is administered to participants with IBS. The study will include clinician and participant ratings of depression and anxiety pre- and post-drug-session, monitor and participant ratings of subjective drug effects during and after each drug session.

This study comprises approximately a 28-day screening period (Days 28 to 1). After screening and enrollment, participants will be randomized to an immediate treatment group or a delayed treatment group ("waitlist control" condition).

Participants in the immediate treatment group will proceed directly into three weeks of baseline and preparation (Days 1 to 18), a 2-dose administration period (Days 22 and 37), integration (Days 23, 30, 38, and 45), the End of Therapy (EOT) visit (Day 52). Participants in the delayed treatment group will wait 8 weeks after enrollment before beginning the study interventions and neuroimaging assessments. As a safety precaution, participants in the delayed treatment group will be assessed weekly via telephone calls or in-person visits during the wait period (i.e., telephone assessments during post-randomization weeks 1, 2, 3, 4, 5, 6, and 7; in-person assessment during post-randomization week 8) to assess suicide risk to determine if intervention is warranted. During week 8, IBS symptoms will also be assessed. At the end of the delay period, all participants in the delayed treatment group will complete the same intervention as the participants in the immediate treatment group.

Validated and commonly used assessment tools will be used to evaluate symptoms at baseline and repeatedly after each session. The weekly average of worst daily pain score and weekly stool frequency and consistency for the 7 days immediately prior to EOT visit will be assessed for change from baseline and at the 3-, 6 , and 12- month follow-up visits (Days 120, 240, 365).

Eligibility Criteria

Inclusion

Inclusion Criteria:

Age

Participant must be 21 to 64 years of age, inclusive, at the time of signing the informed consent form.

Type of Participant and Disease Characteristics

Participant has a body mass index (BMI) between 18.5 and 29.9
Have a clinical diagnosis of IBS (any subtype) as defined by the Rome IV clinicalcriteria:
Abdominal pain at least 4 days per month over at least 2 months associated with oneor more of the following: i. Related to defecation ii. A change in frequency of stool iii. A change in form (appearance) of stool iv. After appropriate evaluation, the symptoms cannot be fullyexplained by another medical condition
Have "treatment resistant" IBS (Rajagopalan 1997) by having all of the following:
symptoms for more than 12 months by history
received adequate explanation and reassurance for symptoms as documented by agastroenterologist in the medical record. This means the patient's primarygastroenterologist will document that they have conducted an evaluation that iswithin appropriate standards of practice to exclude other medical conditions,and that in their opinion irritable bowel syndrome is the most appropriatediagnosis. The patient's primary gastroenterologist will also document thatthey have discussed this evaluation and diagnosis with the patient.
tried at least one dietary intervention by history
tried at least one pharmacologic agent for at least six weeks by history
Have attempted a gut-brain behavior therapy for at least six weeks by history
Concurrent psychotherapy is allowed if the type and frequency of the therapy hasbeen stable for at least 2 months prior to screening and is expected to remainstable during participation in the study.
Participant must not use tobacco or other nicotine containing products (e.g., vapepens) by history.
Participant must be medically stable as determined by screening for medical problemsvia a personal interview and/or, a medical questionnaire, and an ECG, within 1 monthof starting active intervention (performed during screening).
Participant must agree to consume approximately the same amount ofcaffeine-containing beverage (e.g., coffee, tea, cola) that he/she consumes on ausual morning, before arriving at the research unit on the mornings of TRP 8802session days. If the participant does not routinely consume caffeinated beverages,he/she must agree to not do so on the TRP 8802 session day
Participant must agree to refrain from using any psychoactive drugs, includingalcoholic beverages and nicotine, within 24 hours before and after each TRP 8802administration. The exception is caffeine.
Participant must agree to not take triptan medications (e.g., sumatriptan) within 72hours before and after each TRP 8802 administration.
Participant must agree to not take sildenafil (Viagra®), tadalafil, or similarmedications within 72 hours before and after each TRP 8802 administration.
Participant must agree to not take any pro re nata (PRN) medications on the morningsof TRP 8802 sessions.
Participant must agree that for 7 days before each TRP 8802 session, he/she willrefrain from taking any nonprescription medication, cannabis, nutritionalsupplement, or herbal supplement except when approved by the Principal Investigator.Exceptions will be evaluated by the Principal Investigator and will includeacetaminophen, non-steroidal anti-inflammatory drugs, osmotic laxatives, stimulantlaxatives, secretagogues such as linaclotide and lubiprostone, birth control,thyroid hormones, and common doses of vitamins and minerals.
Participant must have at least a high school level of education or equivalent (e.g.,General Educational Development [GED] Test).
Participant must demonstrate ability to track abdominal pain and stool frequency andconsistency daily in the ePRO system.
Participant must demonstrate ability to wear watch with heart rate trackingcapability for daily heart rate tracking.
Participant must be willing to attempt fMRI scan and EEG. Sex andContraceptive/Barrier Requirements
Contraceptive use by women and men should be consistent with local regulationsregarding the methods of contraception for those participating in clinical studies.Adequate birth control methods include intrauterine device,injected/implanted/intravaginal/transdermal hormonal method, oral hormones plus abarrier contraception, abstinence, vasectomized sole partner, or double barriercontraception. Subjects will be excluded if they cannot use highly effective birthcontrol for any reason. If a potential subject lives in an area where localregulations preclude the use of adequate contraception (intrauterine device,injected/implanted/intravaginal/transdermal hormonal method, oral hormones plus abarrier contraception, abstinence, vasectomized sole partner, or double barriercontraception), study enrollment will not be allowed.
If a participant is opting for abstinence as their birth control method, onlytrue/total abstinence is permitted. Periodic abstinence (e.g., calendar,ovulation, symptothermal, post-ovulation methods), lactational amenorrhea, andwithdrawal are not acceptable. Counseling regarding the importance ofmaintaining abstinence, and the potential risks of exposure to a developingembryo or fetus will be provided during the preparatory sessions during thePreparation 1 session, Integration 1 session, and during Deep Phenotyping 2.
Females of reproductive potential must agree to use effective birth control forthe duration of active intervention (defined as the time from the Baseline [deep phenotyping] visit until 6 months and 3 days (for female subjects) afterDeep Phenotyping/EOT visit. Female subjects must agree to not donate eggs, orparticipate in in vitro fertilization for the duration of the recommendedcontraceptive use of the trial.
Sexually active male participants and/or their female partners must agree touse effective birth control for the duration of active intervention (defined asthe time from the Baseline [deep phenotyping] visit until the 3 months and 3days (for male subjects) after Deep Phenotyping/EOT visit of the maleparticipant. Male participants must also agree not to donate sperm for theduration of active intervention. Informed Consent
Participant has provided informed consent as described in Appendix 1 which includescompliance with the requirements and restrictions listed in the informed consentform (ICF) and in this protocol.

Exclusion

Exclusion Criteria:

Medical Conditions

Participant has the following vital sign measurements (taken after 5 minutes ofsitting down) during screening visit: SBP>139 mmHg, DBP > 89 mmHg, and/or HR > 90bpm
Participant has a history of valvular heart disease reported during screening
Participant has a history of pulmonary hypertension reported during screening
Participant has moderate to severe hepatic impairment (Child Pugh Class B and C) asdetermined by presence of ascites or encephalopathy and scoring of albumin,bilirubin, and INR on screening labs
Participant has one of the following gastrointestinal medical conditions:inflammatory bowel disease (ulcerative colitis or Crohn's disease), celiac disease,chronic idiopathic constipation, or eosinophilic esophagitis reported duringscreening
Participant has had (within the past 1 year) a cardiovascular condition such ascoronary artery disease, stroke, angina, uncontrolled hypertension, a clinicallysignificant ECG abnormality (e.g., atrial fibrillation), prolonged QTc interval (i.e., QTc > 450 msec), artificial heart valve, or transient ischemic attackreported during screening
Participant has epilepsy with a history of seizures reported during screening
Participant has insulin-dependent diabetes reported during screening
Participant is taking an oral hypoglycemic agent and has a history of hypoglycemia.
Participant has active auto-immune disease (e.g., lupus, rheumatoid arthritis)reported during screening
Participants has any clinically significant lab abnormalities per a complete bloodcount and metabolic panel (e.g., elevated liver enzymes) at time of screening, andadditional screening labs to exclude organic disease within the past two years.Please see screening in Section 4.2. Cutoffs requiring exclusion from the study arelisted below: Lab Panel Test Cutoff for Exclusion CBC White Blood Cell Count >17 K/uL CBCHemoglobin <11.5 g/dL CBC Platelets <150 K/uL Metabolic Panel Sodium <130 or >150Metabolic Panel Potassium <3.2 or > 5.5 Metabolic Panel CO2 <23 or >32 BUN >40 (2XULN) Creatinine >1.3 Liver Enzymes Direct bilirubin >1.0 Liver Enzymes AST > 80 (2xULN) Liver Enzymes ALT > 55 (ULN) Clotting Factors INR >4
Participant has a current or past history of meeting Diagnostic and StatisticalManual of Mental Disorders, 5th edition (DSM-5) criteria for schizophrenia spectrumor other psychotic disorders (except substance/medication-induced or due to anothermedical condition), or bipolar I or II disorder measured via SCID-5 and SCID-5-PD.
Participant has a current or past history (within 1 year) of meeting DSM-5 criteriafor a moderate or severe alcohol, tobacco, or other drug use disorder (excludingcaffeine) measured via relevant questions from the SCID-5 during screening
Participant meets Rome IV criteria for the diagnosis of centrally mediated abdominalpain syndrome (CAPS). Other co-morbid Rome IV diagnoses will not be exclusioncriteria.
Participant has a history of a medically significant suicide attempt, meaning asuicide attempt leading to an emergency room visit or inpatient hospitalization forany length of time.
Participant does not meet institutional guidelines and safety measures for MRI (e.g., has metal in the body or severe claustrophobia) Prior/Concomitant Therapy
Participant is taking psychoactive prescription medication (e.g., opioids, tramadol,benzodiazepines) on a regular basis (i.e., more than 2 times a week).
Participant is currently taking an antidepressant or neuromodulator, includingSSRIs, SNRIs, and TCAs. Participants will also be required to refrain from usingantidepressant medications through the completion of primary outcome assessments.Note: if a participant self-initiates a medication taper with the consent andsupport of their physician, they can re-screen after the appropriate time period.
Participant has taken any antidepressant medication for at least 2 weeks (or atleast 4 weeks for fluoxetine) prior to the Screening visit.
Participant is currently taking on a regular (e.g., daily) basis any medicationshaving a primary centrally-acting serotonergic effect, including monoamine oxidaseinhibitors (MAOIs). For individuals who have intermittent or PRN use of suchmedications, TRP 8802 sessions will not be conducted until at least 5 half-lives ofthe agent have elapsed after the last dose.
Subjects taking serotonin-acting dietary supplements (such as 5-hydroxy-tryptophanor St. John's wort) due to the potential for their interaction with psilocybin andincreased safety risks.
Subjects taking prohibited medications. The list of prohibited medications includesantihypertensive medications (any ACE-I, ARB, beta blocker, or calcium channelblocker), UGT1A9 or 1A10 inhibitors (e.g., regorafenib, rifampicin, phenytoin,eltrombopag, mefenamic acid, diflunisal, niflumic acid, sorafenib, isavuconazole,deferasiroxor, ginseng) and aldehyde or alcohol dehydrogenase inhibitor (e.g.,disulfiram).
Participant does not agree to refrain from cannabis use and the use of all otherpsychoactive medications and drugs of abuse during the study
Participant is currently taking prohibited drugs of abuse, includingmethamphetamine, illicit opioids (e.g., heroin), cocaine, 3,4-methylenedioxymethamphetamine (Ecstasy/Molly), or hallucinogens (e.g., mescalineor peyote).
Participant has any use of hallucinogens in the past 6 months or has had a totallifetime hallucinogen use of 10 or more times.
Participant tests above 0.02% blood alcohol content on breath alcohol testing and/orpositive for cocaine, methamphetamine, or opioids on urine drug testing.
Participant has a psychiatric condition judged to be incompatible with establishmentof rapport or safe exposure to TRP 8802. Prior/Concurrent Clinical Study Experience
Participant is currently in another clinical trial. Diagnostic assessments
Participant has a significant suicide risk as defined by:
suicidal ideation as endorsed on items 4 or 5 on the C-SSRS within the pastyear at Screening or at Baseline; or
suicidal behaviors within the past year; or
clinical assessment of significant suicidal risk during participant interviewsOther Exclusions
Participant is pregnant (as indicated by a positive urine pregnancy test assessed atScreening and before the TRP 8802 session) or nursing.
Participant is a WOCBP and sexually active, or a man and sexually active, and notpracticing an effective means of birth control.
Participant has a confirmed first- or second-degree relative with schizophreniaspectrum or other psychotic disorders (except substance/medication-induced or due toanother medical condition), or bipolar I or II disorder.
Participant is unable to complete 10/14 days of ePRO tracking during run-in period.

Study Design