Dronabinol for Pain and Inflammation in Adults Living With Sickle Cell Disease

Study Overview
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Brief Summary
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This study is designed to address the feasibility of a randomized, double masked, cross-over study of dronabinol as a palliative agent in the treatment of pain, inflammation, and other complications of sickle cell disease (SCD).

Detailed Description
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The Primary Hypothesis is that such a study will be feasible as defined by subject adherence to study medication and study procedures and avoidance of other cannabinoid containing substances during the trial period as well as by ability to mask subjects and investigators to treatment assignment Secondary hypotheses are: Dronabinol will: Reduce patient-reported pain interference Reduce patient-reported pain scores and change patient-reported pain quality. Reduce use of opioid pain medications. Improve patient-reported stiffness, nausea and vomiting, sleep, mood, anxiety, and social functioning. Reduce markers of inflammation.

Official Title
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Dronabinol for Pain and Inflammation in Adults Living With Sickle Cell Disease

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Drug: Dronabinol 2.5 MG
* Drug: Microcrystalline cellulose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female Age ≥18 years, able to understand and sign the informed consent form Clinical diagnosis of SCD (HbSS, HbSC, HbSβ+; Thal, HbSβ0Thal, HbS variants) Baseline score of 60 or lower on the ASCQ-Me 7-day pain interference domain Willing to abstain from marijuana, medical and illicit, during study weeks 1 through 6. For patients currently receiving hydroxyurea and/or L-glutamine, on a stable dose(s) for at least 3 months For patients currently on a chronic red blood cell transfusion program, on such a program for at least 3 months Exclusion Criteria: Known intolerance to dronabinol, sesame oil, or marijuana Patients with a diagnosis or medical history of any psychiatric disorder with psychosis Presence of any concomitant medical condition, or use of concomitant medication, that, in the Investigator's opinion, may place the subject at increased risk of side effects of dronabinol. Pregnant or nursing women If a woman capable of becoming pregnant, unwilling to use a medically accepted form of birth control for the duration of study participation. Accepted forms include oral contraception or vaginal ring, medroxyprogesterone, contraceptive implants, intrauterine device, or patch, surgical sterilization, total abstinence. We have not included a similar restriction for men as the current FDA approval includes no such restriction.

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: Treatment
Intervention Model: Crossover Assignment
Interventional Model Description: This is a randomized, double blind, cross-over study of dronabinol compared to placebo
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dronabinol, Then Placebo<br>Participants will take 2.5 mg of Dronabinol for 2 weeks, 1 week washout and then take 2 weeks of placebo (microcrystalline cellulos). Subjects will take up to 8 capsules daily of the treatment daily during each phase. | Drug: Dronabinol 2.5 MG<br>* Subjects will take dronabinol daily during 2 week dosing period separated by a one week washout period.<br>Drug: Microcrystalline cellulose<br>* Subjects will take placebo daily during 2 week dosing period separated by a one week washout period.<br>* Other names: Placebo;|
| Experimental: Placebo, Then Dronabinol<br>Participants will take placebo (microcrystalline cellulos) for 2 weeks, 1 week washout and then take 2.5 mg of Dronabinol for 2 weeks. Subjects will take up to 8 capsules daily of the treatment daily during each phase. | Drug: Dronabinol 2.5 MG<br>* Subjects will take dronabinol daily during 2 week dosing period separated by a one week washout period.<br>Drug: Microcrystalline cellulose<br>* Subjects will take placebo daily during 2 week dosing period separated by a one week washout period.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility will be defined by ability to mask patients and investigators to treatment assignment and adherence | Feasibility will be defined by ability to mask patients and investigators to treatment assignment and adherence which will be defined in 3 ways. | 1 year | 
| Adherence | Adherence to study drug will be assessed with weekly pill counts and urine toxicology. | 1 year | 
| Avoidance | Avoidance of other cannabinoid containing substances will also be defined using urine toxicology once at the end of each treatment period and once at the end of the wash out period. | 7 weeks | 
| Adherence to other study proceedures | Adherence to other study procedures will be defined as percent of visits attended, percent of urine and serum studies collected and percent of patient reported outcomes and daily pain severity and pain unpleasentness journals returned. | 7 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient reported 7-day pain interference | The primary endpoint for this study will be second treatment week 7-day pain impact as measured by the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) 7-day pain impact domain. ASCQ-Me domains are validated to measure pain and other quality of life outcomes in adults with Sickle Cell Disease (SCD) of all genotypes. The published mean for the validated scores is 50 and the standard deviation is 10.56 Lower scores represent more severe symptoms. When the validation cohort was placed into tertiles of severity, the tertile with most severe disease had a mean pain score of 53, the middle tertile had a score of 49, and the least severe disease tertile had a mean score of 46. This suggests that a change of 4 has clinical significance and a change of 7 has even more clinical significance. We have chosen a priori to define a difference in pain impact score of 5 points as showing superiority. | 7 days | 
| Patient Pain Severity | Daily reports of pain severity on a numeric rating scale of 0-10 with 0 representing the least severe pain (no pain) and 10 representing the most severe pain. | end of 2nd week | 
| Patient Pain Unpleasantness | Daily reports of pain unpleasantness on a numeric rating scale of 0-10 with 0 representing the least pain unpleasantness (no unpleasantness) and 10 representing the most unpleasant pain. | end of 2nd week | 
| PROMIS (Patient Reported Outcomes Measurement Information System) Nociceptive Pain Severity | Nociceptive pain quality as defined by the patient report outcome measurement information system (PROMIS) nociceptive pain quality 5a scale. All PROMIS scores will be presented as T scores. The T score is a standardized score with a mean of 50 and a standard deviation of 10. The value of 50 represents the score of the average field test respondent. | end of 2nd week | 
| PROMIS Neuropathic Pain Severity | Neuropathic pain quality as defined by the patient report outcome measurement information system (PROMIS) neuropathic pain quality 5a scale.All PROMIS scores will be presented as T scores. The T score is a standardized score with a mean of 50 and a standard deviation of 10. The value of 50 represents the score of the average field test respondent. | end of 2nd week | 
| PROMIS Gastrointestinal Nausea short form measure | PROMIS short form Gastrointestinal Nausea and vomiting 4a. All PROMIS scores will be presented as T scores. The T score is a standardized score with a mean of 50 and a standard deviation of 10. The value of 50 represents the score of the average field test respondent. | end of 2nd week | 
| PROMIS short form for emotional distress anxiety 8a. | PROMIS short form Gastrointestinal Nausea and vomiting 4a. All PROMIS scores will be presented as T scores. The T score is a standardized score with a mean of 50 and a standard deviation of 10. The value of 50 represents the score of the average field test respondent. | end of 2nd week | 
| Adult Sickle Cell Quality (ASCQ)-Me short form measures of emotional impact | Each ASCQ-Me score is reported on the same standardized scale with a mean of 50 and a standard deviation of 10. The value of 50 represents the health score of the average field test respondent. | end of 2nd week | 
| Adult Sickle Cell Quality (ASCQ)-Me short form measure of sleep impact | Each ASCQ-Me score is reported on the same standardized scale with a mean of 50 and a standard deviation of 10. The value of 50 represents the health score of the average field test respondent. | end of 2nd week | 
| Adult Sickle Cell Quality (ASCQ)-Me short form measure of stiffness impact | Each ASCQ-Me score is reported on the same standardized scale with a mean of 50 and a standard deviation of 10. The value of 50 represents the health score of the average field test respondent. | end of 2nd week | 
| Adult Sickle Cell Quality (ASCQ)-Me short form measure of social functioning impact | Each ASCQ-Me score is reported on the same standardized scale with a mean of 50 and a standard deviation of 10. The value of 50 represents the health score of the average field test respondent. | end of 2nd week | 
| Opioid Utilization | Secondary comparisons will be made between subjects on dronabinol to themselves on placebo for patient reported outcomes for opioid use. Opioid utilization will be based on reports of opioids dispensed obtained from the Connecticut Prescription Monitoring Program. Reports will be in the form of average daily opioids used in oral morphine equivalents. | end of 2nd week | 
| Markers of Inflammation Concentration of white blood cell count differential | Secondary comparisons will be made between subjects on dronabinol to themselves on placebo for differential white blood cell count at the end of the second week of the treatment period. | end of 2nd week | 
| Markers of Inflammation C reactive protein | Secondary comparisons will be made between subjects on dronabinol to themselves on placebo of C reactive protein at the end of the second week of the treatment period. | end of 2nd week | 
| Markers of Inflammation serum tryptase | Secondary comparisons will be made between subjects on dronabinol to themselves on placebo for serum tryptase at the end of the second week of the treatment period. | end of 2nd week | 
| Serum pro-inflammatory cytokines | Secondary comparisons will be made between subjects on dronabinol to themselves on placebo for pro-inflammatory cytokines at the end of the second week of the treatment period. | end of 2nd week | 
| Serum measure of Substance P | Secondary comparisons will be made between subjects on dronabinol to themselves on placebo for Substance P at the end of the second week of the treatment period. | end of 2nd week |