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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Immunity Disorders

Intervention / Treatment
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* Dietary Supplement: N-Acetyl-L-cysteine (NAC)
* Dietary Supplement: Echinacea purpurea
* Dietary Supplement: Curcumin
* Dietary Supplement: Palmitoylethanolamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects meeting all of the following criteria will be considered for admission to the study: Healthy subjects between 60-70 years of age. 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 Have a BMI between18.5-29.9 Agrees not to use any over the counter, prescription, health supplement or dietary supplement from screening until the end of the study period. Agrees to refrain from vaccinations throughout the study period. Able to maintain their current routine level of physical activities throughout the study period 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. 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. Women will be those without child bearing potential Exclusion Criteria: Subjects meeting any of the following criteria will not be eligible for the study: Have a known sensitivity or allergy to any of the study products Self-reported smokers 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 Receipt of a vaccination of any type within 60 days prior to the baseline visit. Difficulty with venipuncture and/or poor venous access Any major surgery within 1 year of study drug administration Anticipated major surgeries or major life events (major travel or change in lifestyle conditions) forecast to occur during the anticipated study periods Blood transfusion within 8 weeks of study drug administration Donation of blood or plasma to a blood bank or clinical study within 8 weeks of study drug administration Any clinically significant abnormalities in vital signs, as judged by the investigator. Hypertension or on blood pressure lowering medication 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. History of prior significant cardiovascular disease, coronary artery disease, cardiovascular surgery, significant valvular disease, heart failure, arrhythmias, sick sinus syndrome or stroke 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 History of immune disorder (such as HIV/AIDS), hepatitis B or hepatitis C, or positive immune disorder diagnosis History of alcohol or substance abuse in the 12 months prior to screening History of cannabis product use, including Cannabidiol (CBD), in the 3 months prior to screening 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.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 8 participants assigned to Palmitoylethanolamide 8 participants assigned to Echinacea purpurea 8 participants assigned to Curcumin 8 participants assigned to N-Acetyl-L-cysteine
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: N-Acetyl-L-cysteine (NAC)<br>600 mg 1 capsule twice daily for 14 days | Dietary Supplement: N-Acetyl-L-cysteine (NAC)<br>* Health Canada Natural Product Number (NPN) 80056946<br>* Other names: NAC;|
| Active Comparator: Echinacea purpurea<br>252 mg 1 capsule twice daily for 14 days | Dietary Supplement: Echinacea purpurea<br>* Health Canada Natural Product Number (NPN) 80093896<br>|
| Active Comparator: Curcumin<br>60 mg 3 capsules once daily for 14 days | Dietary Supplement: Curcumin<br>* Health Canada Natural Product Number (NPN) 80043455<br>|
| Active Comparator: Palmitoylethanolamide<br>400 mg 3 capsules once daily for 14 days | Dietary Supplement: Palmitoylethanolamide<br>* Health Canada Natural Product Number (NPN) 80097472<br>|

What is the study measuring?
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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 |