Mechanisms of Cannabidiol in Persons With MS: the Role of Sleep and Pain Phenotype

Pain Clinical Trial

Official title:

Mechanisms of Cannabidiol (CBD) in Persons With Multiple Sclerosis (MS): the Role of Sleep and Pain Phenotype

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05269628
• Other study ID #: HUM00190734
• Secondary ID: 1R01AT011341-01
• Status: Recruiting
• Phase: Phase 2
• Start date: March 25, 2022
• Est. completion date: June 2026

Study information

• Verified date: December 2023
• Source: University of Michigan
• Contact: David Johnson
• Phone: 734-615-9650
• Email: johnsodj[@]umich.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this research study is to compare the effects of cannabidiol (CBD), tetrahydrocannabinol (THC), or both, on sleep and pain in persons with multiple sclerosis (MS). Little is known about how CBD and/or THC may help sleep, reduce pain, or perhaps even treat pain through better sleep.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 166
• Est. completion date: June 2026
• Est. primary completion date: June 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Patients with clinically definite MS (those who are on a disease modifying therapy must be on a stable dose without evidence of liver toxicity for at least 3 months);

2. Presence of chronic pain defined as moderate to severe pain for at least 3 months, based on a 0-10 numeric rating scale (NRS);

3. Willingness to maintain stable analgesic regimen during study period;

4. Recent serum aspartate transaminase, alanine transaminase, and bilirubin testing within 90 days of screening;

Exclusion Criteria:

1. Current shift work sleep disorder, or narcolepsy diagnosed with polysomnography and multiple sleep latency test;

2. History of MS relapse within the last 30 days prior to screening (participants will be considered eligible after the 30-day window);

3. Pain due to cancer;

4. Pregnancy or breastfeeding;

5. Current cannabinoid use (participants may be reconsidered for inclusion after 30-day washout) and/or unwillingness to abstain from cannabinoids in any form from 30 days prior to the study of the study drugs and until the last follow up phone call at the end of the study (30 - 37 days after taking the last dose of the study drug).

6. Unwillingness to use contraception from screening until the end of drug treatment

7. Current suicidal ideation (SI) with intent and/or plan; these individuals will be assessed by a study psychologist and referred for urgent mental health treatment as indicated;

8. Current severe depression as indicated by a PHQ-9 score of = 17 that includes indicators of significant depressed mood (sum of items #1 and #2 = 5).

9. History of mania or schizophrenia diagnosis

10. Known hypersensitivity to cannabinoids in general, or Epidiolex® or Dronabinol specifically or its excipients (e.g., sesame oil)

11. History of the following cardiovascular conditions: recent myocardial infarction or stroke (last 6 months prior to screening), unstable angina, left ventricular hypertrophy, mitral valve prolapses, severe coronary artery disease, NYHA class III or IV congestive heart failure.

12. History severe hepatic impairment (must have blood AST = 2.0x ULN, ALT = 2,0x ULN, and bilirubin = 1.5x ULN within the last 90 days (AST, ALT, bilirubin testing will be required within 90 days of screening);

13. History of seizure disorder (recurrent, unprovoked seizures not explained by a known reversible cause) or history of certain types of head injury that could cause an increased risk of seizures;

14. History of prescription or illicit drug abuse (such as cocaine, amphetamine, methamphetamine, heroin);

15. Current risk for alcohol misuse as indicated by a score of = 8 on the Alcohol Use Disorders Identification Test (AUDIT) self-report measure.

16. Current warfarin, valproate or clobazam use.

17. Current use of known moderate or strong inhibitors of CYP3A4 [topical ketoconazole, and temporary (<= 4 week) oral courses of clarithromycin, fluconazole and itraconazole will be allowed].

18. Current use of strong inducers of CYP3A4 or CYP2C19 (does not include glucocorticoids or modafinil/armodafinil, which are permitted),

19. Current use of moderate or strong inhibitors/inducers of CYP2C9, and narrow therapeutic index drugs (e.g., cyclosporine, amphotericin B).

20. Current use of known non-minor Sensitive CYP2C19 Substrates, with the exception of some proton pump inhibitors (e.g., esoprazole, omeprazole)), periodic self-limited courses of diazepam (e.g., for MRI sedation) and submaximal doses of some antidepressant class medications (e.g., citalopram, and escitalopram), which will be permitted by the discretion of the treating neurologist PI.

21. Refusal to avoid grapefruit or grapefruit products during the study treatment interval.

22. Current use of opioids (tramadol permitted).

23. Employed as a commercial driver or employed in an occupation that involves extreme heights or use of heavy machinery.

24. History of car crashes or near-crashes due to untreated sleepiness that has led to near-misses in the past 6 months.

25. Cognitive dysfunction as indicated by >=3 errors on the six-item cognitive screener

26. Expanded Disability Status Scale (EDSS) score >=8.0.

27. Blood pressure at screening above 180 mmHg systolic and/or 120 mmHg diastolic, or below 90 mmHg systolic and or 60 mmHg diastolic, or history of syncope related to orthostatic hypotension;

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

29. Any other treatment or medical, neurological, sleep, or psychiatric condition that, in the opinion of the investigators, could affect participant safety or eligibility.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Pain
• Sclerosis
• Sleep

Intervention

Drug:
• Cannabidiol (CBD)
Epidiolex® doses will be 0.5 mL twice daily during the first seven days of active treatment and 1 mL twice daily (b.i.d.) for the remaining treatment.
• Tetrahydrocannabinol (THC)
The drug dose will be 2.5 mg b.i.d. during the first 7 days of active treatment, and 5 mg b.i.d. for the following treatment.
• Placebo CBD
Placebo solution will be taken twice per day, using the same dosing regimen as described for Epidiolex®.
• Placebo THC
Placebo capsules will be taken twice per day in the same schedule and manner as active dronabinol.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Tiffany J. Braley, MD, MS	National Center for Complementary and Integrative Health (NCCIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean change in sleep bout length	Measured with in-laboratory polysomnography, reported as average length of continuous bouts of sleep, for each sleep stage and total sleep (in minutes).	Baseline, 12 weeks
Primary	Change in Walsh Spectral Entropy	Measured with in-laboratory polysomnography, computed from EEG sleep stage data to quantify hypnogram regularity (dimensionless, values range from 0-1)	Baseline, 12 weeks
Primary	Change in Transition Entropy	Measured with in-laboratory polysomnography. Entropy measure computed from sleep stage transition matrix that quantifies hypnogram regularity (dimensionless, values range from 0-1)	Baseline, 12 weeks
Primary	Change of center of activity	Measured with in-laboratory polysomnography. Weighted mean temporal location over the night of all 30 second epochs scored as N3 and Rapid eye movement (REM) sleep	Baseline, 12 weeks
Primary	Change in sleep rhythmicity	Measured by actigraphy. Probability of being in the same sleep/wake state 24h apart	Baseline, 12 weeks
Primary	Change in sleep regularity	Measured by actigraphy in hours.	Baseline, 12 weeks
Primary	Change in sleep continuity and duration	Measured by actigraphy in minutes to obtain time in wakefulness after sleep onset (WASO) and total sleep time.	Baseline, 12 weeks