Bioavailability and Pharmacokinetic Measures of H. Procumbens Extract

Study Overview
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Brief Summary
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Study will define the bioavailability and short term pharmacokinetics of the principal secondary metabolites of a aqueous-ethanolic extract of H. procumbens in non-enteric and enteric capsules.

Detailed Description
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The study(n = 12) will use a one-dose design to measure bioavailability and pharmacokinetic properties of an aqueous extract of H. procumbens containing 100mg harpagoside. Plasma levels of harpagoside, harpagide, verbascoside, and 8-p-coumarylharpagide will be measured for 24 hours with blood collections taken at timed intervals.

Official Title
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Study to Establish the Bioavailability and Pharmacokinetic Measures of H. Procumbens Extract in Humans

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Drug: Enteric coated Devil's Claw
* Drug: Non-enteric coated Devil's Claw


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:- adult (at least 18 years of age); diagnosed with knee osteoarthritis (OA) ; body mass index (BMI) of less than 40; willing to use only the study product, and Tramadol or Tylenol as a rescue pain medication over the course of their participation in the study; willing and able to monitor blood glucose levels if diabetic; willing to abstain from caffeine-containing drinks and food before coming into a study visit; able to read and understand English and have the cognitive capacity to give consent; willing to abstain from use of the following during participation in the study: prescription and over-the-counter non-steroidal anti-inflammatory medications, (e.g., aspirin, ibuprofen, Advil, Motrin, Nuprin, Naproxen, etc.); any dietary supplements (St. John's Wort, etc.); and, grapefruit and/or products containing it. Exclusion Criteria:- cardiovascular disease, previous myocardial infarction, stent, coronary artery bypass graft (CABG), arrhythmia, high or low blood pressure; recurrent stomach upset, or gastric or duodenal ulcers; gallstones or gall bladder disease (cholelithiasis); liver or kidney disease; alcohol use of more than two drinks per day on a regular basis; Coumadin or anti-platelet drug use; at risk for respiratory depression, history of seizures, or taking drugs that reduce the seizure threshold or may increase the risk for development of serotonin syndrome; pregnant or breast feeding, or intention to become pregnant during the study; pronounced allergies, or known allergy to study product or corn starch (placebo); have had an injection to treat OA within the past three months; currently taking NSAIDs, unless they are willing to stop for a 1-week wash-out period; currently on a selective serotonin reuptake inhibitor (SSRI) but are poorly stabilized, or have evidence of suicidal ideation and/or suicide attempts in the past year; and, reported use during the 7 days prior to study drug administration of: prescription and over-the-counter medications (e.g., NSAIDs), and any dietary supplements; grapefruit and/or its products; and, St. John's Wort.

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Interventional Model Description: Pharmacokinetic
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Enteric coated Devil's Claw<br>H. procumbens 100 mg in enteric coated capsules | Drug: Enteric coated Devil's Claw<br>* Enteric coated capsules containing Devil's Claw extract with 100mg harpagoside<br>* Other names: Harpagophytum procumbens;|
| Active Comparator: Non-enteric coated Devil's Claw<br>H. procumbens 100 mg in non-enteric coated capsules | Drug: Non-enteric coated Devil's Claw<br>* Non-enteric coated capsules containing Devil's Claw extract with 100mg harpagoside<br>* Other names: Harpagophytum procumbens;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal concentration level of Devil's Claw metabolites, Cmax (ng/ml) | Blood will be drawn at predefined intervals following administration of one dose of study drug | 0.5 hour, 1 hour, 2 hours, 2.5 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 12 hours | 
| Time to reach Cmax (h) | Blood will be drawn at predefined intervals following administration of one dose of study drug | 0 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours | 
| Determination of terminal half-life of Devil's Claw, t 1/2 (h) | Blood will be drawn at predefined intervals following administration of one dose of study drug | 0 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in plasma levels of harpagoside | Blood will be drawn for Devil's Claws metabolites at Visit 2 | 24 hours after dose of Devil's Claw | 
| Change in plasma levels of harpagide | Blood will be drawn for Devil's Claws metabolites at Visit 2 | 24 hours after dose of Devil's Claw | 
| Change in plasma levels of verbascoside | Blood will be drawn for Devil's Claws metabolites at Visit 2 | 24 hours after dose of Devil's Claw | 
| Change in levels of 8-p-coumarylharpagide | Blood will be drawn for Devil's Claws metabolites at Visit 2 | 24 hours after dose of Devil's Claw |