Bioavailability and Pharmacokinetic Measures of H. Procumbens Extract

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Drug: Enteric coated Devil's Claw; Drug: Non-enteric coated Devil's Claw

Detailed Description

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.

• Study Type: Interventional
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Columbia, Missouri, United States, 65211
      • Univ of Missouri Health Care Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Missouri-Columbia
• Investigators: Principal Investigator: William Folk, PhD, Univ of Missouri

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2021
• Primary Completion (Anticipated): July 31, 2021
• Study Completion (Anticipated): August 31, 2021

Study Registration Dates

• First Submitted: August 16, 2018
• First Submitted That Met QC Criteria: August 16, 2018
• First Posted (Actual): August 21, 2018

Study Record Updates

• Last Update Posted (Actual): May 26, 2022
• Last Update Submitted That Met QC Criteria: May 19, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: 2010425; US NIH Grant 7R21AT009086 (Other Grant/Funding Number: NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No