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

Osteoarthritis, Knee Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04620512
• Other study ID #: HUM00180986
• Secondary ID: 1K01DA0492191R01
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: January 2021
• Est. completion date: October 2025

Study information

• Verified date: November 2020
• Source: University of Michigan
• Contact: Anna Piasecki
• Phone: 734-998-7020
• Email: panna[@]umich.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 two weeks 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).

This studies primary hypothesis is that CBD alone will exert a peripheral anti-inflammatory effect shown through decreases in circulating levels of Interleukin-6 (IL-6), THC alone will modify central nervous system (CNS) pain processing via decreased insula to Default Mode Network (DMN) connectivity, and CBD plus THC will do both.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. completion date: October 2025
• Est. primary completion date: October 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 75 Years

Eligibility

Inclusion Criteria:

• 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 of the knee;

• No use of cannabis or CBD in the past month per self-report;

• No more than 4 uses of cannabis or CBD in the past year per self-report.

• Chronic knee pain, be defined as moderate to severe knee pain that is greater or equal to (=) 4 on average using a 0-10 numeric rating scale (NRS) for = 6-month duration.

• additional participants must meet the study inclusion for pain after the 2 weeks of treatment.

• Right handed

• Self-reported normal visual acuity or correctable (with corrective lenses- glasses or contacts) to at least 20/40 for reading instructions in the MRI and visual sensitivity testing

• No contraindications to MRI (for example, metal implants);

• Willingness to refrain from pain medications such as NSAIDs and acetaminophen for 12 hours prior to neuroimaging and QST

• Willingness to refrain from alcohol and nicotine before QST and neuroimaging (alcohol and nicotine consumption is allowed after testing is completed)

• Willingness to refrain from physical activity or exercise that would cause significant muscle and/or joint soreness for 48 hours prior to testing (routine exercise or activity that does not lead to soreness is acceptable);

• No use of adjunctive pain medications or stable chronic daily use of adjunctive pain medications (excluding opioids);

• Able to lie still on their back for 1-1.5 hours during MRI;

• Females of reproductive potential must agree to use acceptable birth control from the screening visit and until the completion study drug administration. Sexually active male participants and/or their female partners must agree to use effective contraception during study drug treatment of the male participant. Male participants may also agree not to donate sperm during study drug treatment.

Exclusion Criteria:

• Individuals receiving or applying for compensation or disability and other aspects associated with potential secondary gain per self-report;

• Previous total knee arthroplasty;

• Planned total knee arthroplasty within the time frame of the study;

• Severe physical impairment (e.g., blindness, deafness, paraplegia);

• Co-morbid medical conditions that may significantly impair physical functional status (e.g., history of non-skin malignancy, or autoimmune disorder);

• Illicit drug use (other than cannabis, see below) per self-report and/or drug screen;

• Current opioid use (excepting tramadol) per self-report and/or drug screen;

• Current valproate, clobazam, or warfarin use per self-report or medical records;

• Current use of moderate or strong inhibitors of cytochrome p450 (CYP) enzymes CYP3A4 and CYP2C19, strong inducers of CYP3A4 or CYP2C19, moderate or strong inhibitors/inducers of CYP2C9, and narrow therapeutic index drugs (e.g., cyclosporine, amphotericin B). Participants will also not be allowed to start using these drugs during the study period if they wish to stay in the study;

• Self-reported allergies to sesame oil or cannabis/cannabinoids;

• Self-reported medical or psychiatric conditions that in the judgment of study personnel would preclude participation in this study (e.g., schizophrenia, malignancy, psychosis, suicidal ideation, history of substance abuse; note that stable anxiety and depression are NOT exclusions);

• Pregnant or nursing;

• Liver failure;

• Self-reported liver cirrhosis;

• Self-reported hepatitis;

• Self-reported uncontrolled diabetes;

• Blood pressure at screening above 180 systolic and/or 120 diastolic;

• Resting heart rate at screening less than 50 bpm or greater than 100 bpm;

• Elevated liver enzymes and bilirubin (measured via blood test at screening):

• Serum total bilirubin = 2.5 mg/dL; or,

• ALT or AST = 3xULN; or,

• Alkaline phosphatase = 2xULN

• Severe cardiovascular disease (examples: history of myocardial infarction, unstable angina, severe coronary artery disease, congestive heart failure, or severe valvular abnormalities) that is self-reported by patient or by medical record;

• Severe claustrophobia precluding MRI;

• Unable to fit in or lie comfortably in MRI;

• Diagnosed peripheral neuropathy;

• Current, recent (within the last 6 months), or habitual use of artificial nails or nail enhancements. (Artificial nails can influence pressure pain sensitivity at the thumbnail);

• Diagnosed or self-reported epilepsy or history of seizures;

• Current head injury or history of head injury (e.g., traumatic brain injury);

• Diagnosed or self-reported visual-evoked migraines;

• Any impairment, activity, behavior, or situation that in the judgment of the study team would prevent satisfactory completion of the study protocol.

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• Placebo
Placebo drug will be taken similarly to the THC and CBD and be matched to keep the trial blinded.
• THC 10 mg/day
Capsules will be taken orally twice daily. Capsules will be 2.5 mg twice a day (b.i.d) during the first week of active treatment, and then 5 mg b.i.d. for the remainder of this treatment.
• CBD 150 mg/day
Epidiolex doses will be 0.37 mL b.id. during the first week of active treatment and then 0.75 mL b.i.d. for the remaining of this treatment.
• CBD 150 mg/day plus THC 10 mg/day
Epidiolex doses will be 0.37 mL b.id. during the first week of active treatment and then 0.75 mL b.i.d. for the remaining of this treatment. Capsules will be taken orally twice daily. Capsules will be 2.5 mg twice a day (b.i.d) during the first week of active treatment, and then 5 mg b.i.d. for the remainder of this treatment.

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan

Sponsors (3)

Lead Sponsor	Collaborator
Richard Harris	National Center for Complementary and Integrative Health (NCCIH), National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Interleukin-6 measured via multiplex assay		2 weeks after treatment and approximately week 14
Primary	Change in insula-default mode network (DMN) connectivity measured via fcMRI	CAN YOU GIVE ME A BRIEF WAY TO EXPLAIN THIS MEASUREMENT? IS IT THE fcMRI or just fMRI? or both? I listed the fcMRI.	2 weeks after treament and approximately week 14