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

Primary Purpose

Sickle Cell Disease

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Dronabinol 2.5 MG
Microcrystalline cellulose
Sponsored by
Yale University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sickle Cell Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Yale New Haven Hospital Smilow Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Dronabinol, Then Placebo

Placebo, Then Dronabinol

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.
Adherence
Adherence to study drug will be assessed with weekly pill counts and urine toxicology.
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.
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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
May 22, 2019
Last Updated
January 21, 2021
Sponsor
Yale University
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1. Study Identification

Unique Protocol Identification Number
NCT03978156
Brief Title
Dronabinol for Pain and Inflammation in Adults Living With Sickle Cell Disease
Official Title
Dronabinol for Pain and Inflammation in Adults Living With Sickle Cell Disease
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Terminated
Why Stopped
Covid-19. Relocation of trainee/investigator. Covid-19.
Study Start Date
July 26, 2019 (Actual)
Primary Completion Date
January 1, 2021 (Actual)
Study Completion Date
January 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Model Description
This is a randomized, double blind, cross-over study of dronabinol compared to placebo
Masking
ParticipantCare ProviderInvestigator
Masking Description
double blinded
Allocation
N/A
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dronabinol, Then Placebo
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo, Then Dronabinol
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Dronabinol 2.5 MG
Intervention Description
Subjects will take dronabinol daily during 2 week dosing period separated by a one week washout period.
Intervention Type
Drug
Intervention Name(s)
Microcrystalline cellulose
Other Intervention Name(s)
Placebo
Intervention Description
Subjects will take placebo daily during 2 week dosing period separated by a one week washout period.
Primary Outcome Measure Information:
Title
Feasibility will be defined by ability to mask patients and investigators to treatment assignment and adherence
Description
Feasibility will be defined by ability to mask patients and investigators to treatment assignment and adherence which will be defined in 3 ways.
Time Frame
1 year
Title
Adherence
Description
Adherence to study drug will be assessed with weekly pill counts and urine toxicology.
Time Frame
1 year
Title
Avoidance
Description
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.
Time Frame
7 weeks
Title
Adherence to other study proceedures
Description
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.
Time Frame
7 weeks
Secondary Outcome Measure Information:
Title
Patient reported 7-day pain interference
Description
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.
Time Frame
7 days
Title
Patient Pain Severity
Description
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.
Time Frame
end of 2nd week
Title
Patient Pain Unpleasantness
Description
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.
Time Frame
end of 2nd week
Title
PROMIS (Patient Reported Outcomes Measurement Information System) Nociceptive Pain Severity
Description
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.
Time Frame
end of 2nd week
Title
PROMIS Neuropathic Pain Severity
Description
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.
Time Frame
end of 2nd week
Title
PROMIS Gastrointestinal Nausea short form measure
Description
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.
Time Frame
end of 2nd week
Title
PROMIS short form for emotional distress anxiety 8a.
Description
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.
Time Frame
end of 2nd week
Title
Adult Sickle Cell Quality (ASCQ)-Me short form measures of emotional impact
Description
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.
Time Frame
end of 2nd week
Title
Adult Sickle Cell Quality (ASCQ)-Me short form measure of sleep impact
Description
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.
Time Frame
end of 2nd week
Title
Adult Sickle Cell Quality (ASCQ)-Me short form measure of stiffness impact
Description
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.
Time Frame
end of 2nd week
Title
Adult Sickle Cell Quality (ASCQ)-Me short form measure of social functioning impact
Description
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.
Time Frame
end of 2nd week
Title
Opioid Utilization
Description
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.
Time Frame
end of 2nd week
Title
Markers of Inflammation Concentration of white blood cell count differential
Description
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.
Time Frame
end of 2nd week
Title
Markers of Inflammation C reactive protein
Description
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.
Time Frame
end of 2nd week
Title
Markers of Inflammation serum tryptase
Description
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.
Time Frame
end of 2nd week
Title
Serum pro-inflammatory cytokines
Description
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.
Time Frame
end of 2nd week
Title
Serum measure of Substance P
Description
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.
Time Frame
end of 2nd week

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Susanna Curtis, MD
Organizational Affiliation
Yale University School of Medicine Oncology Section
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yale New Haven Hospital Smilow Cancer Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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