Short-term Impact of Cyplexinol® on Self-reported Joint Pain

Study Overview
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Brief Summary
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In this study, the impact of 900 mg Cyplexinol® taken daily on joint pain over a period of 15 days in comparison with a placebo will be determined using a cross-over double blind design with a 13 day wash out period. In addition, we will measure cytokine production and related variables during the two hour after subjects ingest a single dosage of Cyplexinol® or placebo on days 1 and 15.

Detailed Description
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Chronic inflammation can induce joint pain, which is a common problem among adult men and women. ZyCal Bioceuticals is a manufacturer of natural ingredients and finished nutritional supplements to support bone and joint health in humans. The core ingredient in all ZyCal products is Cyplexinol® (a Bone Morphogenetic Protein [BMP] Complex). BMP complexes have been shown to activate mesenchymal stem cells to help the body regenerate osteoblasts and chondrocytes. BMPs were initially identified in the 1970's as osteogenic factors which stimulate activation, proliferation, and differentiation of osteoprogenitor cells by binding BMP receptors and subsequent signaling through the SMAD pathway. BMPs have also been shown to reduce inflammation and promote healthy inflammatory signaling in joints and other tissues. Cyplexinol® is delivered in the dietary supplement called Ostinol™, which has been safely used in oral form by thousands of people since 2007 for bone and joint health. Currently Cyplexinol® is considered a dietary supplement ingredient and has been awarded GRAS (generally recognized as safe). Studies have been conducted to evaluate the safety and efficacy of Cyplexinol® as a dietary supplement for joint health (Garian, 2012; Scaffidi, 2017). Dosages of 150mg Cyplexinol® have been compared to a placebo (negative control) alone or in combination with glucosamine /chondroitin in randomized controlled trials for 4 -12 weeks. Endpoints examined have included joint stiffness, inflammation, pain, and overall quality of life. However, to date, no short-term studies have been conducted using Cyplexinol®, nor have any acute studies evaluated the impact of this agent on immune function. In this study, the impact of 900 mg Cyplexinol® taken daily on joint pain over a period of 15 days in comparison with a placebo will be determined using a cross-over double blind design with a 13 day wash out period. In addition, we will measure cytokine production and related variables during the two hour post ingestion period after subjects ingest a single dosage of Cyplexinol® or placebo on days 1 and 15.

Official Title
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Short-term Impact of Cyplexinol® on Inflammatory Status and Related Measures in Men and Women With Self-reported Joint Pain

Conditions
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Joint Pain

Intervention / Treatment
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* Dietary Supplement: Cyplexinol
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: body mass index (BMI) between 18-29.9 kg/m2 (not obese) no consumption of alcohol-containing beverages within 48 hours of testing experiencing self-reported joint pain with a minimum pain rating of 3/10 for at least the past 30 days engaged in structured exercise 2 or more days per week for the past 6 months or longer a negative verbal pre-study drug screen (alcohol abuse, amphetamines, benzodiazepines, cocaine, opioids, phencyclidine, barbiturates, cotinine), no history of use of illicit drugs or other substances of abuse within 12 months of the screening visit Exclusion Criteria: pregnant tobacco user active infection or illness of any kind rheumatic or osteoarthritic diagnosis Using anti-inflammatory medicines, pain medications, or dietary supplements (or not willing to cease for one-month prior to participation and throughout study)

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Double-blind, randomized, control
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cyplexinol<br>900 mg daily (2 capsules) for 15 days | Dietary Supplement: Cyplexinol<br>* partially hydrolyzed Collagen and its associated proteins including Bone Morphogenetic Proteins (BMPs)<br>|
| Placebo Comparator: Placebo<br>2 capsules daily for 15 days | Other: Placebo<br>* Maltodextrin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TNF-alpha | TNF-alpha measured in blood | baseline of day 1 | 
| TNF-alpha | TNF-alpha measured in blood | baseline of day 15 | 
| TNF-alpha | TNF-alpha measured in blood | 60 min after treatment ingestion of day 1 | 
| TNF-alpha | TNF-alpha measured in blood | 60 min after treatment ingestion of day 15 | 
| TNF-alpha | TNF-alpha measured in blood | 120 min after treatment ingestion of day 1 | 
| TNF-alpha | TNF-alpha measured in blood | 120 min after treatment ingestion of day 15 | 
| IL-6 | IL-6 measured in blood | baseline of day 1 | 
| IL-6 | IL-6 measured in blood | baseline of day 15 | 
| IL-6 | IL-6 measured in blood | 60 min after treatment ingestion of day 1 | 
| IL-6 | IL-6 measured in blood | 60 min after treatment ingestion of day 15 | 
| IL-6 | IL-6 measured in blood | 120 min after treatment ingestion of day 1 | 
| IL-6 | IL-6 measured in blood | 120 min after treatment ingestion of day 15 | 
| IL-10 | IL-10 measured in blood | baseline of day 1 | 
| IL-10 | IL-10 measured in blood | baseline of day 15 | 
| IL-10 | IL-10 measured in blood | 60 min after treatment ingestion of day 1 | 
| IL-10 | IL-10 measured in blood | 60 min after treatment ingestion of day 15 | 
| IL-10 | IL-10 measured in blood | 120 min after treatment ingestion of day 1 | 
| IL-10 | IL-10 measured in blood | 120 min after treatment ingestion of day 15 | 
| IL-1beta | IL-1beta measured in blood | baseline of day 1 | 
| IL-1beta | IL-1beta measured in blood | baseline of day 15 | 
| IL-1beta | IL-1beta measured in blood | 60 min after treatment ingestion of day 1 | 
| IL-1beta | IL-1beta measured in blood | 60 min after treatment ingestion of day 15 | 
| IL-1beta | IL-1beta measured in blood | 120 min after treatment ingestion of day 1 | 
| IL-1beta | IL-1beta measured in blood | 120 min after treatment ingestion of day 15 | 
| osteocalcin | osteocalcin measured in blood | baseline day 1 | 
| osteocalcin | osteocalcin measured in blood | baseline day 15 | 
| osteocalcin | osteocalcin measured in blood | 60 min after treatment ingestion of day 1 | 
| osteocalcin | osteocalcin measured in blood | 60 min after treatment ingestion of day 15 | 
| osteocalcin | osteocalcin measured in blood | 120 min after treatment ingestion of day 1 | 
| osteocalcin | osteocalcin measured in blood | 120 min after treatment ingestion of day 15 | 
| alkaline phosphatase | alkaline phosphatase measured in blood | baseline day 1 | 
| alkaline phosphatase | alkaline phosphatase measured in blood | baseline day 15 | 
| alkaline phosphatase | alkaline phosphatase measured in blood | 60 min after treatment ingestion of day 1 | 
| alkaline phosphatase | alkaline phosphatase measured in blood | 60 min after treatment ingestion of day 15 | 
| alkaline phosphatase | alkaline phosphatase measured in blood | 120 min after treatment ingestion of day 1 | 
| alkaline phosphatase | alkaline phosphatase measured in blood | 120 min after treatment ingestion of day 15 | 
| Bone Morphogenetic Protein | Bone Morphogenetic Protein measured in blood | baseline day 1 | 
| Bone Morphogenetic Protein | Bone Morphogenetic Protein measured in blood | baseline day 15 | 
| Bone Morphogenetic Protein | Bone Morphogenetic Protein measured in blood | 60 min after treatment ingestion of day 1 | 
| Bone Morphogenetic Protein | Bone Morphogenetic Protein measured in blood | 60 min after treatment ingestion of day 15 | 
| Bone Morphogenetic Protein | Bone Morphogenetic Protein measured in blood | 120 min after treatment ingestion of day 1 | 
| Bone Morphogenetic Protein | Bone Morphogenetic Protein measured in blood | 120 min after treatment ingestion of day 15 | 
| Joint pain visual analog scale | A 100mm visual analog scale will be used to assess joint pain. Scores range from 0 (subject strongly disagreeing with prompt) to 100 (strongly agree). | Day 1 of treatment | 
| Joint pain visual analog scale | A 100mm visual analog scale will be used to assess joint pain. Scores range from 0 (subject strongly disagreeing with prompt) to 100 (strongly agree). | Day 15 of treatment | 
| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) | The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68) with 0 being none and high values being most. | Day 1 of treatment | 
| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) | The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68) with 0 being none and high values being most. | Day 15 of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dietary intake | Dietary intake of subjects for 3-days prior to testing days analyzed using Food Processor Pro software for total calories, macro- and micro-nutrient composition | Day 1 of treatment | 
| Dietary intake | Dietary intake of subjects for 3-days prior to testing days analyzed using Food Processor Pro software for total calories, macro- and micro-nutrient composition | Day 15 of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cyplexinol, Inflammation