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

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).

Study Overview

• Status: Terminated
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: Dronabinol 2.5 MG; Drug: Microcrystalline cellulose

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale New Haven Hospital Smilow Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Dronabinol, Then Placebo; 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; Subjects will take dronabinol daily during 2 week dosing period separated by a one week washout period.; Drug: Microcrystalline cellulose; Subjects will take placebo daily during 2 week dosing period separated by a one week washout period.; Other Names: Placebo
EXPERIMENTAL: Placebo, Then Dronabinol; 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; Subjects will take dronabinol daily during 2 week dosing period separated by a one week washout period.; Drug: Microcrystalline cellulose; Subjects will take placebo daily during 2 week dosing period separated by a one week washout period.; Other Names: Placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Principal Investigator: Susanna Curtis, MD, Yale University School of Medicine Oncology Section

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 26, 2019
• Primary Completion (ACTUAL): January 1, 2021
• Study Completion (ACTUAL): January 1, 2021

Study Registration Dates

• First Submitted: May 22, 2019
• First Submitted That Met QC Criteria: June 5, 2019
• First Posted (ACTUAL): June 6, 2019

Study Record Updates

• Last Update Posted (ACTUAL): January 26, 2021
• Last Update Submitted That Met QC Criteria: January 21, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Inflammation; Anemia, Sickle Cell; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Psychotropic Drugs; Hallucinogens; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Dronabinol
• Other Study ID Numbers: 2000021179

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes