Randomized Trial of Curcumin to Reduce Mucositis in Autologous Transplant Setting

  • STATUS
    Recruiting
  • End date
    May 16, 2023
  • participants needed
    190
  • sponsor
    Tata Memorial Centre
Updated on 30 May 2021

Summary

Mucositis is a very common complication in bone marrow transplant setting. It is a result of injury to the gut caused by high dose chemotherapy. Currently there are no universal protocols that have been accepted as a standard to prevent and treat mucositis in the transplant setting. Post transplant upto 80% of patients suffer from a severe mucositis. Proinflammatory cytokines play a major role in the development of mucositis. Interventions that decrease the levels of these cytokines may be beneficial in preventing mucositis. This study is aimed at evaluating the role of curcumin in reducing cytokine levels and the incidence and duration of mucositis in patients undergoing autologous stem cell transplantation.

Description

Mucositis is an inevitable side-effect of intensive conditioning therapy used for hematopoietic stem cell transplantation and affects the quality of life of patients undergoing transplant. The incidence of oral mucositis (WHO grades 3/4 ) with certain myeloablative conditioning regimens has been reported in up to 90% with range of severe mucositis (WHO grade 3/4) from 10 to 78%. Pro-inflammatory cytokines such as IL-1, IL-6, IL-8, IL-17, TNF-, TGF-B, IFN- and certain prostaglandins play a central role in its pathogenesis. Transcription factors such as NF-kappa B, modify the genetic expression of these cytokines and enzymes which are critical in producing tissue damage.

A number of agents and methods have been investigated to prevent or reduce mucositis in transplant setting. Some of them are amifostine, caphasol, palifermin, cryotherapy, chlorhexidine, glutamine, GM-CSF, histamine, misoprostol, laser therapy and traumeel, but only palifermin and cryotherapy have shown significant benefit.

Curcumin, polyphenol derivative with low toxicity profile, is commonly used in India for its anti-inflammatory actions. Curcumin inhibits various inflammatory cytokines through inhibition of Nuclear Factor Kappa- . It is derived from the plant Curcuma longa. In vitro studies have shown potent anti-inflammatory activity at concentrations of 1 umol/L.

The investigators conducted the first study evaluating the role of curcumin on oral mucositis in transplant setting. In this pilot study (n=40), patients who received curcumin lozenges (n=30) had decreased levels of salivary TGF-, IL-17 and serum PGE2 compared to patients who did not receive the curcumin lozenges (n=10). Patients who received the curcumin lozenges had higher levels of serum IL-8 which is a prohealing cytokine. The incidence of grade 3 and 4 oral mucositis and diarrhea was less in those who received curcumin lozenges. Curcumin lozenges were also well tolerated and none of the 30 patients who were administered curcumin developed any treatment related grade 3/4 toxicity. This encouraging data is the basis of the current phase III randomized study comparing curcumin lozenges to placebo, to assess the ability of curcumin to reduce the incidence and duration of oral mucositis in patients undergoing autologous bone marrow transplantation.

The formulation being used is a Solip Lipid Curcumin microParticle (SLCP). The formulation is developed by Pharmanza Herbals Pvt. Ltd., Gujarat, India. Gota et al reported a phase I clinical trial of SLCP where upto 4 grams of the formulation containing 20-30% curcumin was evaluated for safety and pharmacokinetics in patients with high-risk osteosarcoma (Ref). The SLCP formulation showed oral bioavailability of curcumin with linear pharmacokinetics. Average peak plasma concentration of 41 ng/mL was observed at the highest dose level of 4g. All doses were well tolerated and no adverse events were observed. Based on these observations (on safety and bioavailability), and the reported anti-inflammatory properties of curcumin, it was envisaged that it could be potentially useful for the prophylaxis and treatment of oral mucositis following high-dose chemotherapy.

Details
Condition Stomatitis
Treatment Placebo Lozenges, Curcumin Lozenges
Clinical Study IdentifierNCT04896164
SponsorTata Memorial Centre
Last Modified on30 May 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Male or female patients 18 years and above
Patients who give written informed consent
Patients with performance status - 0,1 or 2 (ECOG scale)
Patients receiving any of the following high dose chemotherapy regimens for autologous transplant in any indicated malignant disease
Melphalan- 200 mg/m2 or more (MEL-200 mg/m2)
Busulfan and Melphalan (BuMEL)
Carmustine (BCNU), Etoposide, Cytosine Arabinoside and Melphalan ( BEAM)
Patients who have creatinine clearance > 50 ml/min
Patients with serum bilirubin levels < 2mg/dl. and serum liver enzymes (ALT or AST or both) lesser than 5 times the upper limit of normal value

Exclusion Criteria

Patients who are on NSAIDs, aspirin, antioxidants or systemic steroids for more than 3 months and the last dose taken within the last one week
Patients being treated for active infection at the time of starting high dose chemotherapy
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note