Immune Diversity Response to Oral Dosing of Nutritional Health Products in Healthy Participants

A Open Label, Multi-Dose, Multi-Period Exploratory Clinical Trial to Test Immune Diversity Response to Oral Dosing of Approved Nutritional Health Products at Approved Doses to Healthy Volunteers

A Phase IV, open-label, adaptive, 4-arm, multi-dose, single-centre, exploratory trial to assess the immune diversity response to oral administration of licensed Natural Health Products, in healthy adults, 60-70 years of age.

Study Overview

• Status: Completed
• Conditions: Immunity Disorders
• Intervention / Treatment: Dietary supplement: N-Acetyl-L-cysteine (NAC); Dietary supplement: Echinacea purpurea; Dietary supplement: Curcumin; Dietary supplement: Palmitoylethanolamide

Detailed Description

In this study, the effect of licensed Natural Health Products (NHP) on immune response-related/antibody diversity parameters will be measured. Immune repertoire changes will be measured by genetic sequencing of segments of mRNA in the participant's blood that correspond to the coding regions for the Complementarity Determining Region - 3 (CDR-3) of T- and B-cell surface receptors. CDR-3 receptor segments are the highly variable recognition elements of the T- and B-cell receptors responsible for the recognition of foreign cells and other entities. This recognition step is an early step in the adaptive immune response.

Each of the four arms in the study contains 8 participants and each arm is assigned one NHP: Palmitoylethanolamide, or Echinacea purpurea, or Curcumin, or N-Acetyl-L-cysteine (NAC).

Longitudinal changes in immune diversity and dynamics, as indicated by changes in the CDR-3 sequence information will be measured over five timeframes in an four week period.

Baseline dynamics and diversity will be measured by comparing the results from participant visits 2 and 3. The impact of the NHP will be evident from comparing results between Visits 3 and 4. Finally, the impact of stopping the NHP dosing will be evident in comparing the results from Visit 5 to those of 4, 3, and 2. The techniques being used to analyze the sequence information are exploratory.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5S2B7
      • Dicentra

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects meeting all of the following criteria will be considered for admission to the study:

  1. Healthy subjects between 60-70 years of age.
  2. Availability of the subject for one of the forecasted study periods and willingness of the subject to adhere to protocol requirements, as evidenced by a signed Informed Consent Form
  3. Have a BMI between18.5-29.9
  4. Agrees not to use any over the counter, prescription, health supplement or dietary supplement from screening until the end of the study period.
  5. Agrees to refrain from vaccinations throughout the study period.
  6. Able to maintain their current routine level of physical activities throughout the study period
  7. Willing and able to agree to the requirements and restrictions of this study (including but not limited to: not consuming more than 2 standard alcoholic beverages a day [A standard alcoholic beverage is defined as 12 ounces of beer, five (5) ounces of wine, or 1.5 ounces of liquor]), not consuming cannabis products of any type.
  8. In good health as determined by lack of clinically significant abnormalities in health assessments (history, physical examination, laboratory tests) performed at screening as judged by the physician.
  9. Women will be those without child bearing potential

Exclusion Criteria:

• Subjects meeting any of the following criteria will not be eligible for the study:

  1. Have a known sensitivity or allergy to any of the study products
  2. Self-reported smokers
  3. Receipt or use of an investigational product in another research study within 30 days prior to Baseline (Visit 2) or currently participating in another research study
  4. Receipt of a vaccination of any type within 60 days prior to the baseline visit.
  5. Difficulty with venipuncture and/or poor venous access
  6. Any major surgery within 1 year of study drug administration
  7. Anticipated major surgeries or major life events (major travel or change in lifestyle conditions) forecast to occur during the anticipated study periods
  8. Blood transfusion within 8 weeks of study drug administration
  9. Donation of blood or plasma to a blood bank or clinical study within 8 weeks of study drug administration
  10. Any clinically significant abnormalities in vital signs, as judged by the investigator.
  11. Hypertension or on blood pressure lowering medication
  12. Subjects with medical conditions that might interfere with participation in the study or interpretation of the study results. These include serious chronic diseases such as diabetes, neurologic or psychiatric disease (including any previous suicidal symptoms or suicide attempts), cardiovascular disease, gastrointestinal disease, pulmonary disease, cancer, autoimmune diseases, immunodeficiencies, hepatic or renal diseases.
  13. History of prior significant cardiovascular disease, coronary artery disease, cardiovascular surgery, significant valvular disease, heart failure, arrhythmias, sick sinus syndrome or stroke
  14. History of clinically significant cerebrovascular, metabolic, pulmonary, neurological, hematological, autoimmune, endocrine disorders, including individuals with Type I or Type II diabetes, or other clinically significant medical condition that, in the opinion of the Investigator, may preclude safe study participation
  15. History of immune disorder (such as HIV/AIDS), hepatitis B or hepatitis C, or positive immune disorder diagnosis
  16. History of alcohol or substance abuse in the 12 months prior to screening
  17. History of cannabis product use, including Cannabidiol (CBD), in the 3 months prior to screening
  18. Any other medical or social condition that, in the judgment of the investigator, would preclude provision of informed consent, make participation in the study unsafe, complicate interpretation of study outcome data or otherwise interfere with achieving the study objectives.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: N-Acetyl-L-cysteine (NAC); 600 mg 1 capsule twice daily for 14 days	Dietary supplement: N-Acetyl-L-cysteine (NAC); Health Canada Natural Product Number (NPN) 80056946; Other Names: NAC
ACTIVE_COMPARATOR: Echinacea purpurea; 252 mg 1 capsule twice daily for 14 days	Dietary supplement: Echinacea purpurea; Health Canada Natural Product Number (NPN) 80093896
ACTIVE_COMPARATOR: Curcumin; 60 mg 3 capsules once daily for 14 days	Dietary supplement: Curcumin; Health Canada Natural Product Number (NPN) 80043455
ACTIVE_COMPARATOR: Palmitoylethanolamide; 400 mg 3 capsules once daily for 14 days	Dietary supplement: Palmitoylethanolamide; Health Canada Natural Product Number (NPN) 80097472

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in participants T & B cell Diversity Index (D50) from day 0 to day 29	D50 measures changes in frequency distributions of complementarity-determining region 3 (CDR3) in order to identify correlations between treatment and immune diversity. Diversity Index (D50) is a measure of the CDR3 diversity in the first half of the immune repertoire when looking at the frequency distributions. Additional bioinformatic analysis methods will be applied including Shannon Equitability Index and Antigen-specific Lymphocyte Identification by Clustering of Expanded Sequences.	4 weeks

Collaborators and Investigators

• Sponsor: Immunoflex Therapeutics Inc.
• Collaborators: University of British Columbia; Dicentra Inc.
• Investigators: Principal Investigator: Gurinder Raj, MD, Dicentra

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 10, 2021
• Primary Completion (ACTUAL): May 1, 2021
• Study Completion (ACTUAL): May 20, 2021

Study Registration Dates

• First Submitted: January 13, 2022
• First Submitted That Met QC Criteria: February 7, 2022
• First Posted (ACTUAL): February 16, 2022

Study Record Updates

• Last Update Posted (ACTUAL): February 16, 2022
• Last Update Submitted That Met QC Criteria: February 7, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Expectorants; Acetylcysteine; N-monoacetylcystine; Curcumin; Palmidrol
• Other Study ID Numbers: IMFX.CT1.002

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