Randomized Trial of Curcumin to Reduce Mucositis in Autologous Transplant Setting

NCT ID: NCT04896164

Last Updated: 2023-11-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 190 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-16
• Study Completion Date: 2025-05-16

Brief 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.

Detailed 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-α, TGF-B, IFN-γ 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- β. 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-β, 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.

Conditions

Oral Mucositis (Ulcerative)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: QUADRUPLE

Study Groups

Investigational arm

Patients in the investigational arm will receive curcumin lozenges (4 gm BD containing 400 mg curcumin BD) as prophylaxis from two days prior to receiving high dose chemotherapy .

Group Type: EXPERIMENTAL

Curcumin Lozenges

Intervention Type: DRUG

Curcumin lozenges (each containing 100 mg of curcumin) will be given at a dose of 4 lozenges (total dose 400 mg curcumin) BD. Formulation is Solid Lipid Curcumin Particle (SLCP). Oral curcumin lozenges will be given from two days prior to receiving high dose chemotherapy till day+28 of transplant.

Control arm

patients in the control arm will receive matching placebo lozenges from two days prior to receiving high dose chemotherapy

Group Type: PLACEBO_COMPARATOR

Placebo Lozenges

Intervention Type: OTHER

Placebo lozenges will be given from two days prior to receiving high dose chemotherapy till day+28 of transplant.

Interventions

Curcumin Lozenges

Curcumin lozenges (each containing 100 mg of curcumin) will be given at a dose of 4 lozenges (total dose 400 mg curcumin) BD. Formulation is Solid Lipid Curcumin Particle (SLCP). Oral curcumin lozenges will be given from two days prior to receiving high dose chemotherapy till day+28 of transplant.

Intervention Type: DRUG

Placebo Lozenges

Placebo lozenges will be given from two days prior to receiving high dose chemotherapy till day+28 of transplant.

Intervention Type: OTHER

Other Intervention Names

Longvida (Pharmanza Herbal Pvt Ltd.)

Eligibility Criteria

Inclusion Criteria

1. Male or female patients 18 years and above.

2. Patients who give written informed consent

3. Patients with performance status - 0,1 or 2 (ECOG scale)

4. Patients receiving any of the following high dose chemotherapy regimens for autologous transplant in any indicated malignant disease.

1. Melphalan- 200 mg/m2 or more (MEL-200 mg/m2)

2. Busulfan and Melphalan (BuMEL)

3. Carmustine (BCNU), Etoposide, Cytosine Arabinoside and Melphalan ( BEAM)

5. Patients who have creatinine clearance > 50 ml/min

6. 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

1. 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.

2. Patients being treated for active infection at the time of starting high dose chemotherapy.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tata Memorial Centre

OTHER

Sponsor Role: lead

Responsible Party

Dr Navin Khattry

Professor and BMT convener

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Navin Khattry, MD, DM

Role: PRINCIPAL_INVESTIGATOR

Tata Memorial Centre Advanced Centre for Treatment, Research and Education in Cancer

Locations

Tata Memorial Centre

Navi Mumbai, Maharashtra, India

Site Status: RECRUITING

Countries

India

Central Contacts

Navin Khattry, MD, DM

Role: CONTACT

nkhattry@gmail.com

022-27405000 ext. 5034

Facility Contacts

Navin Khattry, MD, DM

Role: primary

nkhattry@gmail.com

022-24705000 ext. 5034

Other Identifiers

CTRI/2018/09/015846

Identifier Type: REGISTRY

Identifier Source: secondary_id

900503

Identifier Type: -

Identifier Source: org_study_id