Cannabinoid Interactions With Central and Peripheral Pain Mechanisms in Osteoarthritis of the Knee

ConditionsOsteoarthritis, Knee Osteoarthritis of the Knee

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age21-75

SponsorSteven E Harte, PhD

About this trial

This clinical trial is being done to better understand how daily treatment with Tetrahydrocannabinol (THC), Cannabidiol (CBD), or the combination of CBD plus THC affects knee osteoarthritis pain and other related symptoms.

Consented participants will have a screening period and visit (up to 30 days to treatment start). If participants pass the screening phase, they will be randomly assigned to take one of the investigational study drugs. For this study, participants will not know when or if they are taking CBD, THC, THC plus CBD, and when or if taking placebo.

Clinical pain will be assessed at multiple times throughout the study, and eligibility will be re-assessed at two weeks into the treatment period. It is possible that subjects will not be able to participate in the study after 14 days of of treatment. The treatment period will take approximately 16 weeks and then a follow-up period for approximately 2 weeks. In addition to treatment, participants will have clinical assessments, blood draws, questionnaires, daily pain diaries, sensory testing, as well as have functional connectivity magnetic resonance imaging (fcMRI).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Ability to read and speak English to allow for written informed consent, phenotyping, and patient-reported outcomes measures

Willingness to participate in a drug intervention trial

Diagnosis of osteoarthritis (OA) of the knee by a medical provider (confirmed by checking medical records)

Chronic knee pain, defined as moderate to severe knee pain for ≥ 6-month duration

Disqualifiers

Individuals who are actively applying for or in litigation for compensation or disability and other aspects associated with potential secondary gain per self-report

Inability to provide written informed consent

Previous total knee arthroplasty

Planned total knee arthroplasty within the time frame of the study

Trial design

Design model

Factorial

Treatments tested in this trial

Placebo
Drug
Placebo drug will be taken similarly to the THC and CBD and be matched to keep the trial blinded. In the event that 2.5 mg capsules of dronabinal capsules become unavailable, an equivalent product will be issued to participants and the comparator and placebo arms will be correspondingly adjusted to preserve blinding. If a participant's dose is not well-tolerated, the participant may initiate dose reductions with the study team. Participants will be instructed to eat a meal or snack greater than one hour after taking study drug.
Cannabidiol (CBD)
Drug
Epidiolex doses will be 0.37 milliliter (mL) for seven days of treatment and then 0.75 mL two times a day (b.i.d) for the remaining days of this treatment. In the event that 2.5 mg capsules of dronabinal capsules become unavailable, an equivalent product will be issued to participants and the comparator and placebo arms will be correspondingly adjusted to preserve blinding. If a participant's dose is not well-tolerated, the participant may initiate dose reductions with the study team. Participants will be instructed to eat a meal or snack greater than one hour after taking study drug.
Tetrahydrocannabinol (Marinol® or generic equivalent (e.g., dronabinol)
Drug
Dronabinol Capsules doses will be 2.5 mg b.i.d. for seven days of treatment and then 5 mg b.i.d. for the remaining days of this treatment. In the event that 2.5 mg capsules of dronabinal capsules become unavailable, an equivalent product will be issued to participants and the comparator and placebo arms will be correspondingly adjusted to preserve blinding. If a participant's dose is not well-tolerated, the participant may initiate dose reductions with the study team. Participants will be instructed to eat a meal or snack greater than one hour after taking study drug.

Treatment groups

200 Participants

are divided into 4 treatment groups

Group A: PlaceboPlacebo comparator 1 intervention

Group B: Cannabidiol (CBD)Experimental treatment 1 intervention

Group C: Tetrahydrocannabinol (THC)Experimental treatment 1 intervention

Group D: CBD plus THCExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

Default mode network (DMN) to insula connectivity via functional connectivity magnetic resonance imaging (fcMRI)

Functional connectivity difference maps of insula to DMN connectivity using Independent Component Analysis and seed based connectivity. A reduction in the Z-score as a result of treatment will serve as the primary outcome measure.

Time frame

Day 15, and approximately day 99 of treatment

Change in pre-post measurements of inflammatory marker IL-6.

Serum IL-6

Time frame

Day 15, and approximately day 99 of treatment

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Steven E Harte, PhD

Lead sponsor

University of Michigan

Sponsor institution

National Center for Complementary and Integrative Health (NCCIH)

Collaborator

National Institute on Drug Abuse (NIDA)

Collaborator

Source ClinicalTrials.gov

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