Micro-Particle Curcumin for the Treatment of Chronic Kidney Disease

NCT ID: NCT02369549

Last Updated: 2021-01-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 518 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2020-05-15

Brief Summary

An investigator initiated pilot trial: two arm, double blind, placebo controlled, randomized, parallel group of approximately 750 patients with chronic kidney disease, and who have evidence of overt proteinuria, will be treated with micro-particle curcumin versus placebo over 24 weeks from start of the investigational medication date (approximately 6 months) to test whether curcumin can slow chronic kidney disease progression in patients. Three 30 mg capsules of micro-particle curcumin will be self-administered once daily in the morning to determine the the safety and efficacy of curcumin relative to placebo in reducing albuminuria and slowing the loss of eGFR.

Detailed Description

Limiting the progression from CKD to end-stage renal disease is one of the most important goals in kidney medicine. The evidence implicating inflammation and fibrosis in that process is strong, and there is abundant mechanistic and animal model data to show that curcumin is a potent inhibitor of both inflammation and fibrosis. Two preliminary randomized trials in human CKD hint at curcumin's enormous therapeutic potential in CKD. The Principal Investigator/Sponsor will rigorously test this potential in a broadly selected sample of up to 750 patients with CKD. Compared to previous studies, this study's results will be generalizable across other etiologies of CKD and with a larger sample size; this study will provide more precise estimates of curcumin's benefits and risks. Also, this study proposes to use a new, micro-particle formulation of curcumin that is highly bioavailable. The Principal Investigator/Sponsor will assess curcumin's effects on three key markers of kidney health that encompass the cardinal functions of the nephron. Positive results from MPAC-CKD will lay solid scientific ground-work for a multi-centre trial capable of testing micro-particle curcumin's effect of the most meaningful outcomes: death and the development of end-stage renal disease.

To ensure that this study will have the necessary adherence and tolerability data, up to 750 patients with proteinuric CKD will be randomly assigned to 90 mg per day of micro-particle curcumin or matching placebo, for a total of 24 weeks (approximately 6 months). In the last few years, new formulations of curcumin have been shown to substantially augment absorption by improving its aqueous solubility. The micro-particle formulation of curcumin is one of these new formulations and is the only curcumin delivery system proven to increase bioavailability. Compared to traditional curcumin, micro-particle curcumin achieves total serum concentrations that are 27 fold higher. In this study, micro-particle curcumin will allow the study team to administer the equivalent of 3000 mg of traditional curcumin (which would require six 500 mg capsules daily), in a single 90 mg capsule. In addition, as opposed to traditional curcumin, there is no requirement to take micro-particle curcumin on a full stomach. The Investigator/Sponsor has selected a dose equivalent to 3 grams per day of curcumin because this is within the range of doses proven safe and effective and it will minimize pill burden by allowing the full daily dose to be achieved by three small 30 mg capsules daily In rare cases, curcumin has been reported to cause minor nausea, headache, diarrhea, yellow stool, and temporary giddiness. All unexpected reactions reported in previous studies were easily managed and happened at higher doses than what will be used in MPAC-CKD.

This study will assess two primary outcomes: the 6-month change in albuminuria, and the 6-month change in eGFR.

Secondary outcomes will include health-related quality of life, glycemic control among patients with diabetes mellitus, and a composite of progressive CKD, ESRD and death. The investigators will also measure serum curcumin levels in the first 30 randomized participants, who will have a 4.5 ml blood sample taken at the 12 week (3 month) visit. This sample will be processed and stored at -80 degrees C. for batch testing for plasma micro-particle curcumin concentrations.

The investigators will conduct a subgroup analysis based on participants 2-year risk of requiring dialysis using the validated Kidney Failure Risk Equation to group patients into a high risk group (10% or greater risk of dialysis within 2 years) and low risk group (<10% risk within 2 years).

Medical history, lab values and vitals will be collected and/or updated at each in-person visit. Each participant will be provided with instructions and study schedule. Participants with diabetes mellitus will be given a home glucose log-book.

Protocol compliance will be tested through pill counts and interviews at each follow-up visit. Side effects will be assessed using standardized case report forms at each visit. Participants will be contacted by telephone one week into the trial and then once every 4 weeks (monthly) for 28 weeks (approximately 7 months) for safety monitoring and reporting and to reinforce importance of compliance. In-person visits will occur at 12 and 24 weeks (approximately 3 and 6 months) after randomization and the start of the investigational medication, at which time investigational medication will be counted and supply replenished. First morning at-home urine specimens will be collected at baseline and again arranged at the in-person visits at 12 and 24 weeks (approximately 3 and 6 months). Participants will also be encouraged to report any events they may experience directly to the coordinator(s) and/or PI.

Participants who withdraw consent to continue treatments, will be encouraged to undergo the planned assessments. Withdrawal at the request of investigators or medical personnel may include, but are not limited to:

1. Symptoms are deemed to be potentially related to the sue of the investigational medication;

2. New diagnosis of exclusion criteria;

3. Inter-current illness not related to the use of the investigational Natural Health Product (NHP) medication;

4. Unacceptable side effects;

5. Death;

6. Improved health status.

Estimated time to complete recruitment: Averaging 136 weeks, approximately 34 months.

Long-term outcomes will be tracked using administrative data housed at The Institute for Clinical Evaluative Sciences (ICES), an independent research facility in Toronto, Ontario. ICES works with the Ontario Ministry of Health and Long-Term Care to study the impact of health care and diseases in Ontario.

A panel of external experts and study investigators will comprise the Steering Committee and will ensure the integrity of the study. They will be responsible for reviewing and acting upon the recommendations of the Data Safety Monitoring Board, amendments to the protocol, oversight of publication and dissemination of study results.

Conditions

Chronic Kidney Disease

Study Design

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

Study Groups

Micro-particle curcumin

Three 30 mg capsules once daily, self-administered for 6 months.

Curcumin is a nutraceutical, which are products isolated or purified from foods. The rhizomes of the plant Curcuma longa produces turmeric, a spice commonly used in Indian cuisine. Turmeric is comprised of three curcuminoids, of which curcumin is the most abundant. Curcumin is a polyphenol molecule that has been investigated for anti-inflammatory and anti-neoplastic properties since the 1970s.

Group Type: ACTIVE_COMPARATOR

Micro-particle Curcumin

Intervention Type: DRUG

as described in Arm

Placebo

Three 30 mg capsules taken once daily, self-administered for 6 months.

Placebo capsules are identical to the curcumin capsules in color, taste, smell, size and shape.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Looks, smells, tastes and feels exactly like the Curcumin capsules.

Interventions

Micro-particle Curcumin

as described in Arm

Intervention Type: DRUG

Placebo

Looks, smells, tastes and feels exactly like the Curcumin capsules.

Intervention Type: DRUG

Other Intervention Names

Theracumin-Pro 300

Eligibility Criteria

Inclusion Criteria

1. eGFR between 15 and 60 ml/min/1.73 m2;

2. Albuminuria, defined by the most recent measurement within the prior 3 months showing either: a) 24-hour urine collection with a minimum of 300 mg of protein, OR b) urinary albumin to creatinine ratio equivalent to a daily excretion of albumin of at least 300 mg;

3. If diabetic, is able and willing to take and record glucose levels at home;

4. If receiving and ACE inhibitor or angiotension II receptor blocker (ARB), the dosage must be stable for 2 weeks prior to screening. Patients not taking and ACE or ARB must have a documented medical contraindication (e.g. hyperkalemia, hypotension);

5. Willing and able to give written informed consent for participation and provide consent for access to medical data according to local data protection laws and regulations.

Exclusion Criteria

1. Life expectancy < 1 year;

2. Known allergy to turmeric or its derivatives (ginger, curry, cumin, or cardamom);

3. Known allergy to ingredients of the study product or placebo (microcrystalline cellulose, vegetarian capsule, vegetable grade magnesium stearate, silica;

4. Pregnant or breastfeeding;

5. Women of child-bearing potential who are not either surgically sterile or not postmenopausal for at least 1 year;

6. Plans for transplantation during the study period;

7. Receipt of hemodialysis or peritoneal dialysis in the past 3 months;

8. Active peptic ulcer disease;

9. Hepatobiliary disease in the past 4 weeks;

10. Evidence of acute kidney injury (>50% increase in serum creatinine in the past 30 days);

11. History of significant bleeding (GI or retroperitoneal bleed requiring transfusion, or any intracranial hemorrhage in the past 6 months);

12. Ongoing use of warfarin;

13. Ongoing treatment with cyclophosphamide, camptothecin, mechlorethamine or doxorubicin;

14. Ongoing use of anti-psychotic medication including haloperidol, aripiprazole, risperidone, ziprasidone, pimozide, and quetiapine;

15. Previous participation in MPAC-CKD;

16. Current participation on another investigational medication trial.

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

Sponsors

The Kidney Foundation of Canada

OTHER

Sponsor Role: collaborator

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Matthew Weir, Nephrologist

Role: PRINCIPAL_INVESTIGATOR

LHSC

Locations

Population Health Research Institute

Hamilton, Ontario, Canada

Kidney Clinical Care Unit

London, Ontario, Canada

University Hospital

London, Ontario, Canada

Victoria Hospital

London, Ontario, Canada

Countries

Canada

References

Weir MA, Walsh M, Cuerden MS, Sontrop JM, Urquhart BL, Lim YJ, Chambers LC, Garg AX. The effect of micro-particle curcumin on chronic kidney disease progression: the MPAC-CKD randomized clinical trial. Nephrol Dial Transplant. 2023 Sep 29;38(10):2192-2200. doi: 10.1093/ndt/gfad037.

Reference Type: DERIVED

PMID: 36849161 (View on PubMed)

Weir MA, Walsh M, Cuerden MS, Sontrop JM, Chambers LC, Garg AX. Micro-Particle Curcumin for the Treatment of Chronic Kidney Disease-1: Study Protocol for a Multicenter Clinical Trial. Can J Kidney Health Dis. 2018 Dec 5;5:2054358118813088. doi: 10.1177/2054358118813088. eCollection 2018.

Reference Type: DERIVED

PMID: 30619615 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

MPAC-CKD

Identifier Type: -

Identifier Source: org_study_id