Effects of Immulina TM Supplements With PASC Patients

Study Overview
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Brief Summary
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This is a multi-site study that will try to determine the effects of Immulina ™, a natural dietary supplement, on blood chemicals associated with inflammation that are often increased in patients with long COVID (also called PASC).

Detailed Description
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This is a randomized, double-blind placebo controlled pilot study designed to determine effect size on altering blood inflammatory biomarkers and anti SARS-CoV-2-specific adaptive response including memory T cell, memory B cells and antiviral antibody titers. The participants will have a variety of clinical manifestations that will include varying degrees of fatigue, cognitive dysfunction and other PASC-related symptoms. Individuals will be randomized by site to receive either Immulina or placebo given daily for 8 weeks followed by a 4 week observation off supplement.

Official Title
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Effect of Immulina Supplements on Inflammatory Biomarkers Correlated With Clinical Symptoms in Patients With Long COVID (PASC)

Conditions
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Post Acute COVID-19 Syndrome

Intervention / Treatment
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* Dietary Supplement: Immulina TM
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females, 18 to 99 years old If female of child bearing potential, using acceptable means of birth control or postmenopausal for at least two years Body temperature between 36.1°C and 37.7°C. Has completed the 4-week washout period (if applicable), i.e., has refrained from using internally-consumed dietary supplements prior to Study Day 1 and through the completion of the study A minimum of 2 hours fasting (except water) prior to all of the blood draws Willing and able (in the opinion of study staff) to comply with all study requirements, including swallowing size 4 capsules (approximately 0.5 long and 0.25 diameter) and having phlebotomy Good written and verbal English skills; able to follow instructions (in the investigator's opinion) Not participating in a clinical study, currently or within the last 30 days Signed informed consent Exclusion Criteria: Pregnant or lactating Digestive tract disorders or conditions, such as (but are not limited to): ulcers, ulcerative colitis, Crohn's disease, gastric bypass, colostomy, ischemic colitis, gastroesophageal reflux disease (GERD), irritable bowel disease (IBD), diverticulitis that would be expected to impact on the oral disposition of the Immulina dietary supplement Existence of any surgical and/or medical condition, significant disease or disorder, or any finding that may, in the judgment of the investigator, put the volunteer at risk or compromise study participation. Any blood-thinning or clotting concomitant medication (prescription anticoagulants) Donation or loss of 400 mL or more of blood within 8 weeks of Study Day 1 or unwilling to abstain from donation of blood during the study Known or suspected allergy or sensitivity to Immulina, cellulose History of drug or alcohol abuse within the last 12 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immulina TM 800 mg/day<br>Immulina Dietary supplementation (200 mg per capsule) 2-200 mg capsules given by mouth in the morning and 2-200 mg capsules given by mouth in the evening for 8 weeks duration | Dietary Supplement: Immulina TM<br>* Immulina TM is a highly standardized extract derived from various preparations of Spirulina, a cyanobacterium, marketed as a dietary supplement and has been utilized in several clinical studies describing its immunopotentiiating properties.<br>* Other names: Spirulina;|
| Placebo Comparator: Placebo<br>inert capsules; 2 capsules given by mouth in the morning and 2 capsules given by mouth in the evening for 8 weeks duration | Dietary Supplement: Placebo<br>* Placebo is inert powder in cellulose capsule that appears identical to Immulina TM capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma IL-6 (Interleukin 6, pg/mL) | Differences in Interleukin 6 from baseline to 12 weeks | 12 weeks | 
| Plasma CRP (C-Reactive Protein, ng/mL) | Differences in C-Reactive Protein from baseline to 12 weeks. | 12 weeks | 
| Plasma D-Dimer, pg/mL | Differences in D-Dimer from baseline to 12 weeks. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PROMIS-29 | Differences in questionnaire PROMIS-29, Domain T-scores PROMIS-29 is a collection of short forms containing a fixed number of items from the same 7 PROMIS domains (physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles and activities, and pain interference) plus a single item on pain intensity. They assess all domains over the past seven days except the Physical Function, which has no timeframe specified. Four questions asked for each of 7 domains, plus the single pain intensity item and scored separately, yielding a total of 7 domain scores. The final score is represented by the T-Score, a standardized score with a mean of 50 and a standard deviation [SD] of 10. High scores mean more of the concept being measured (e.g., more fatigue, more Physical Function). | 12 weeks | 
| FSS | Differences in Fatigue Severity Scale (FSS) questionnaire between baseline to 12 weeks Changes in questionnaire FSS, units on a scale, results that reflect PASC-associated symptoms of fatigue, neurocognitive dysfunction, dyspnea and/or other symptoms. The questionnaire FSS contains nine statements that rate the severity of fatigue symptoms. Respondents rate their fatigue severity during the past seven days using a 7 point rating scale. A low value (e.g.1) indicates strong disagreement with the statement, whereas a high value (e.g.7) indicates strong agreement. A total score of less than 36 suggests that the respondent may not be suffering from fatigue. A total score of 36 or more suggests that the respondent may need further evaluation by a physician. | 12 weeks | 
| SBQ-LC TM | Differences in The Symptom Burden Questionnaire for Long COVID (SBQ-LC TM) questionnaire between baseline to 12 weeks Changes in questionnaire SBQ-LC TM (units on a scale) results that reflect PASC-associated symptoms of fatigue, neurocognitive dysfunction, dyspnea and/or other symptoms . SBQ-LC TM (version 1.0) is a modular instrument measuring patient reported outcomes and is composed of 17 independent scales with promising psychometric properties. Respondents rate their symptom burden during the past seven days using a dichotomous response or 4 point rating scale. Each scale provides coverage of a different symptom domain and returns a summed raw score that can be transformed to a linear (0-100) score. Higher scores represent higher symptom burden. | 12 weeks | 
| SARS-CoV-2-specific antibody responses | Differences in SARS-CoV-2-specific antibody immune responses: Receptor Binding domain (RBD) and Nucleocapsid (NP) antibody responses between baseline and 12 weeks | 12 weeks | 
| SARS-CoV-2-specific immune responses on memory T cell levels | Differences in SARS-CoV-2-specific immune responses on memory T cell levels between baseline and 12 weeks | 12 weeks | 
| SARS-CoV-2-specific immune responses on memory B cell levels | Differences in SARS-CoV-2-specific immune responses on memory B cell levels between baseline and 12 weeks | 12 weeks | 
| Natural Killer cell (NK)-mediated cytotoxicity | NK cell-mediated cytotoxicity is characterized by cytolysis of a CSFE-labeled (K562) by effector cells (NK cells). Labeled K562 are cultured with NK cells for a period of time, then all cells labeled with a live-dead stain, 7-AAD. The cytolytic actively is expressed as the percent dead K562. Difference in cytolytic activity (%dead K562) from baseline to 20 weeks. | 12 weeks | 
| Natural Killer (NK) cell count | Difference in NK cell counts from baseline to 20 weeks. | 12 weeks | 
| Cytolytic T lymphocyte (CTL) number | Difference in CTL cell number from baseline to 20 weeks. | 12 weeks | 
| serum Interferon alpha, pg/mL | Difference in Interferon alpha from baseline to 20 weeks. | 12 weeks | 
| serum Interferon gamma, pg/mL | Difference in Interferon gamma from baseline to 20 weeks. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immulina, Post Acute Covid-19 Syndrome, Inflammation, Natural Dietary Supplement