Pilot Assessment of the Safety of a Combination of Curcumin, Omega-3, and Vitamin D Supplements in ACPA+ Individuals (PASCOD3)

Pilot Assessment of the Safety of a Combination of Curcumin, Omega-3, and Vitamin D Supplements (PASCOD) in ACPA+ Individuals

The goal of this clinical trial is to determine if the level of Anti-cyclic citrullinated peptide antibody (ACPA) is altered after taking curcumin, omega-3, and vitamin D supplements (COD) for 3 months. It will also determine the safety and tolerability of COD in the study population. This trial aims to answer the following questions: Does COD consumption lower the level of ACPA in the study participants? What side effects will participants have after taking COD? This pilot study will have an open label pre-post design and study participants will know that they are using each of the three supplements. Participants will: Take the combination of supplements following an evening meal, for 84 consecutive days. Visit the clinic/study team twice during the study duration on days 0 and 84 for checkups and tests. Keep a diary of study treatment consumption.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Participants
• Intervention / Treatment: Combination product: curcumin, omega-3, and vitamin D (COD)

Detailed Description

Rheumatoid Arthritis (RA) is a prevalent autoimmune disease. Curcumin formulations are recognized for their potent anti-inflammatory effects, mainly targeting NF-kB signaling. Supplementation with Acumin™ has shown significant benefits for RA patients, including pain relief, reduced morning stiffness, and improved joint function, alongside decreases in inflammatory markers and autoantibody levels. In murine arthritis models, a bioavailable curcumin form, combined with a diet rich in vitamin D and omega-3, notably altered disease progression. Therefore, a pilot trial is set for anti-cyclic citrullinated peptide antibody+ (APCA+) individuals without RA. The primary objective of this study will determine if the level of ACPA is altered after taking curcumin, omega-3, and vitamin D (COD) for 3 months. The secondary objective is to determine the safety and tolerability of COD in the study population. Exploratory outcomes will include assessment of joint, symptoms, blood biochemistry and hematology. This study will enroll 50 ACPA+ individuals without RA, aiming for an equal distribution of male and female participants. Participants identified as ACPA+ from the RA Auto-antibody Detection study (RAAD) will undergo eligibility screening. The study will involve open-label administration of ACUMIN™ Turmeric Complex (500 mg), Omega-3 (900 mg), and Vitamin D3 (2500 IU) once daily for 84 consecutive days. Joint examinations will be conducted by a study physician, and blood specimens will be collected by certified phlebotomists at designated sites. Trained personnel will handle questionnaire surveys, anthropometrics, follow-ups, and coordinating visits. Data will be recorded on paper-based CRFs and entered into the secure REDCap database. The trial will take place at Health Sciences Centre (MS7) in Winnipeg for urban participants and in First Nation communities with established research agreements with the team (Norway House First Nation).

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Liam O'Neil, MD, MHSc; Phone Number: +1 (204) 787-1851; Email: liam.oneil@umanitoba.ca

Study Locations

• Canada
  • Manitoba
    • Norway House, Manitoba, Canada, R0B 1B0
      • Norway House Health Centre
      • Principal Investigator: Liam O'Neil, MD
      • Sub-Investigator: Hani El-Gabalawy, MD
      • Sub-Investigator: Dylan MacKay, PhD
      • Contact: Liam O'Neil, MD, MHSc; Phone Number: +1 (204) 787-1851; Email: liam.oneil@umanitoba.ca
      • Sub-Investigator: David Robinson, MD
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • Health Sciences Centre
      • Principal Investigator: Liam O'Neil, MD
      • Sub-Investigator: Hani El-Gabalawy, MD
      • Sub-Investigator: Dylan MacKay, PhD
      • Contact: Liam O'Neil, MD, MHSc; Phone Number: +1 (204) 787-1851; Email: liam.oneil@umanitoba.ca
      • Sub-Investigator: David Robinson, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria

• Verified to be ACPA+ based on serum testing
• Age 18 to 65 years old
• Willing to provide contact information by email, telephone and mailing address
• Participant agrees to take the supplements every day for 84 days
• Female participants of child-bearing potential must be willing to ensure that they use contraception during the trial
• Participant has clinically acceptable laboratory results including routine hematology (CBC) and biochemistry (electrolytes, creatinine, ALT, ALP, GGT, AST, Glucose)
• In the Investigator's opinion, is able and willing to comply with all trial requirements
• If participant is currently taking curcumin, vitamin D and/or omega-3 supplements they must agree to a washout period of at least 1 month prior to the start of the trial.
• Participant agrees to be followed longitudinally in the PRE-RA cohort study, following the completion of this trial.
• Participant is willing and able to give free informed consent and written consent in English, for participation in the trial.

Exclusion Criteria

The participant may not enter the trial if ANY of the following apply:

• Current use of warfarin or similar anticoagulant medication (at the discretion of the P.I.)
• Female participant who is pregnant, lactating or planning pregnancy during the course of the trial
• Female of childbearing potential who is unwilling to use contraception during the trial
• Scheduled elective surgery or other procedures requiring general anaesthesia during the trial
• Any significant disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.
• Concurrent commitment to enroll in another clinical trial
• Regular consumption of vitamin D, omega-3, curcumin supplements and/or curcumin containing product within the last 3 months and unwilling to stop consumption for at least a month prior to the start of the trial.
• Self-report of allergic reaction to fish
• Participants who indicate that they will not consume the treatments on a daily basis
• Current consumption of > 14 drinks per week, (1 drink = 12oz of beer, 5oz of wine or 1.5oz distilled spirits)
• Participants who report they have had viral or bacterial infection in the last 4 weeks (e.g. COVID-19, the flu, a cold, stomach flu, bladder infection, strep throat), and are not fully recovered. Once fully recovered they can participate.
• Participant has been recently vaccinated (past 4 weeks). Participant can continue in the trial 1-month after receiving the vaccination.
• Has vacation/s planned during the trial that may interfere with study monitoring and visit 2. The start of the trial can be adjusted to accommodate planned vacations.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Theracurmin, Vitamin D, and Omega-3; Theracurmin Double Strength: 180 mg/day (oral, 3 tablets of 60 mg taken by mouth) Vitamin D: 2000 IU/day LipoMicel (oral, 1 tablet taken by mouth) Omega-3: 900 mg day (oral, 1 tablet taken by mouth)	Combination product: curcumin, omega-3, and vitamin D (COD); Combination of curcumin, omega-3, and vitamin D supplements (COD). Theracurmin Double Strength/Natural Factors Canada 180 mg/day (oral, 3 tablets of 60 mg taken by mouth) Vitamin D: 2000 IU/day LipoMicel/Natural Factors Canada (oral, 1 tablet taken by mouth) Omega-3: 900 mg day (oral, 1 tablet taken by mouth)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ACPA levels	Anti-cyclic citrullinated peptide antibody (ACPA) levels will be determined with a CCP3.1 ELISA	At Day 0 and Day 84

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side-effect profile of COD	Side-effect profile and prevalence of side-effects of Theracurmin Double Strength, Omega-3, and Vitamin D supplementation will be determined through monitoring the blood results for biochemical and haematology analysis	At Day 0 and Day 84

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Waist circumference measures	Waist circumference in cm using a measuring tape	At Day 0 and Day 84
Weight measures	Weight in kg using a scale	At Day 0 and Day 84
Height measures	Height in cm using a measuring tape	At Day 0 and Day 84
Blood pressure measures	Systolic and diastolic Blood pressure will be measured in mmHg using blood pressure machine	At Day 0 and Day 84
Tender and Swollen Joint Counts (TSJC)	44 tender and swollen joint count will be performed by a rheumatologist	At Day 0 and Day 84
SDAI	Simple Disease Activity Index (SDAI) assessment will be used to determine severity of RA using clinical and laboratory data	At Day 0 and Day 84
CDAI	Clinical Disease Activity Index (CDAI) assessment will be used to determine severity of RA using clinical and laboratory data	At Day 0 and Day 84
DAS28-CRP	The Disease Activity Score (DAS28)-CRP will be determined to assess RA disease activity, calculated once the C-reactive protein (CRP) result is available	At Day 0 and Day 84
Hand grip strength	Hand grip strength will be measured using a Dynamometer in kg, taken in triplicate	At Day 0 and Day 84
RAPID3	Routine assessment of patient index data. Disease activity index calculated from a short and questionnaire	At Day 0 and Day 84
White blood cells (WBC)	WBC measured in x10^9/L	At Day 0 and Day 84
Hemoglobin	Hemoglobin measured in g/L	At Day 0 and Day 84
Platelets	Platelets measured in x10^9/L	At Day 0 and Day 84
Mean platelet volume (MVP)	MVP measured in fL	At Day 0 and Day 84
BUN	The total blood urea concentration in mmol/L	At Day 0 and Day 84
Magnesium	Magnesium measured in mmol/L	At Day 0 and Day 84
Lipid profile	Total cholesterol, LDL, HDL, and Non-fasted triglycerides will be measured in mmol/L	At Day 0 and Day 84
Albumin	Total blood albumin concentration in g/L	At Day 0 and Day 84
Total and direct bilirubin	Total and direct bilirubin is measured in μmol/L	At Day 0 and Day 84
Sodium	Total blood sodium concentration in mmol/L	At Day 0 and Day 84
Potassium	Total blood potassium concentration in mmol/L	At Day 0 and Day 84
Chloride	Total blood chloride concentration in mmol/L	At Day 0 and Day 84
Bicarbonate HCO3	Bicarbonate measured in mmol/L	At Day 0 and Day 84
Creatinine	Total blood creatinine concentration in μmol/L	At Day 0 and Day 84
AST	AST is measured in U/L	At Day 0 and Day 84
ALT	ALT is measured in U/L	At Day 0 and Day 84
ALP	ALP is measured in U/L	At Day 0 and Day 84
GGT	GGT is measured in U/L	At Day 0 and Day 84
Glucose	Total fasted blood glucose concentration in mmol/L	At Day 0 and Day 84
Calcium	Total blood calcium concentration in mmol/L	At Day 0 and Day 84
Phosphate (PO4)	Total blood phosphate concentration in mmol/L	At Day 0 and Day 84
CRP	C-Reactive Protein (CRP)	At Day 0 and Day 84

Collaborators and Investigators

• Sponsor: University of Manitoba
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Liam O'Neil, MD, MHSc, University of Manitoba

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: June 13, 2024
• First Submitted That Met QC Criteria: June 21, 2024
• First Posted (Actual): June 27, 2024

Study Record Updates

• Last Update Posted (Actual): August 1, 2025
• Last Update Submitted That Met QC Criteria: July 29, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Vitamin D; Rheumatoid Arthritis; Omega-3; Curcumin
• Additional Relevant MeSH Terms: Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Antirheumatic Agents; Sensory System Agents; Bone Density Conservation Agents; Analgesics, Non-Narcotic; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Micronutrients; Vitamins; Curcumin; Vitamin D
• Other Study ID Numbers: HS26482 (B2024:059)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No