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

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ClinicalTrials.gov Identifier: NCT03978156
Recruitment Status : Recruiting
First Posted : June 6, 2019
Last Update Posted : July 29, 2019
Sponsor:
Information provided by (Responsible Party):
Yale University

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).

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Drug: Dronabinol Drug: Placebo oral tablet Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: This is a randomized, double blind, cross-over study of dronabinol compared to placebo
Masking: Double (Participant, Care Provider)
Masking Description: double blinded
Primary Purpose: Treatment
Official Title: Dronabinol for Pain and Inflammation in Adults Living With Sickle Cell Disease
Actual Study Start Date : July 26, 2019
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Dronabinol

Arm Intervention/treatment
Experimental: Patient on intervention

Dronabinol capsules are supplied as oblong, soft gelatin capsules containing 2.5 mg of dronabinol.

For masking, one intact active dronabinol capsule will be placed in a capsule shell, back filled with sufficient quantity of microcrystalline cellulose, and closed. The capsules are visually inspected and packed into high density polyethylene (HDPE) bottles.

Drug: Dronabinol
2.5 mg of dronabinol. In the initial 2 to 3 days of each treatment period, study agent dose will be rapidly titrated from a starting dose of dronabinol (or placebo) 5 mg twice daily to a maximum well tolerated dose (MWTD) of up to 10 mg twice daily

Drug: Placebo oral tablet
Placebo oral tablet

Placebo Comparator: Patient on placebo
Matching placebo will be compounded, using a matching empty capsule filled with sufficient quantity of microcrystalline cellulose. The capsules are visually inspected and packed into HDPE bottles.
Drug: Dronabinol
2.5 mg of dronabinol. In the initial 2 to 3 days of each treatment period, study agent dose will be rapidly titrated from a starting dose of dronabinol (or placebo) 5 mg twice daily to a maximum well tolerated dose (MWTD) of up to 10 mg twice daily

Drug: Placebo oral tablet
Placebo oral tablet




Primary Outcome Measures :
  1. Feasibility will be defined by ability to mask patients and investigators to treatment assignment and adherence [ Time Frame: 1 year ]
    Feasibility will be defined by ability to mask patients and investigators to treatment assignment and adherence which will be defined in 3 ways.

  2. Adherence [ Time Frame: 1 year ]
    Adherence to study drug will be assessed with weekly pill counts and urine toxicology.

  3. Avoidance [ Time Frame: 7 weeks ]
    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.

  4. Adherence to other study proceedures [ Time Frame: 7 weeks ]
    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 :
  1. Patient reported 7-day pain interference [ Time Frame: 7 days ]
    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.

  2. Patient Pain Severity [ Time Frame: end of 2nd week ]
    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.

  3. Patient Pain Unpleasantness [ Time Frame: end of 2nd week ]
    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.

  4. PROMIS (Patient Reported Outcomes Measurement Information System) Nociceptive Pain Severity [ Time Frame: end of 2nd week ]
    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.

  5. PROMIS Neuropathic Pain Severity [ Time Frame: end of 2nd week ]
    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.

  6. PROMIS Gastrointestinal Nausea short form measure [ Time Frame: end of 2nd week ]
    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.

  7. PROMIS short form for emotional distress anxiety 8a. [ Time Frame: end of 2nd week ]
    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.

  8. Adult Sickle Cell Quality (ASCQ)-Me short form measures of emotional impact [ Time Frame: end of 2nd week ]
    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.

  9. Adult Sickle Cell Quality (ASCQ)-Me short form measure of sleep impact [ Time Frame: end of 2nd week ]
    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.

  10. Adult Sickle Cell Quality (ASCQ)-Me short form measure of stiffness impact [ Time Frame: end of 2nd week ]
    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.

  11. Adult Sickle Cell Quality (ASCQ)-Me short form measure of social functioning impact [ Time Frame: end of 2nd week ]
    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.

  12. Opioid Utilization [ Time Frame: end of 2nd week ]
    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.

  13. Markers of Inflammation Concentration of white blood cell count differential [ Time Frame: end of 2nd week ]
    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.

  14. Markers of Inflammation C reactive protein [ Time Frame: end of 2nd week ]
    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.

  15. Markers of Inflammation serum tryptase [ Time Frame: end of 2nd week ]
    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.

  16. Serum pro-inflammatory cytokines [ Time Frame: end of 2nd week ]
    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.

  17. Serum measure of Substance P [ Time Frame: end of 2nd week ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03978156


Contacts
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Contact: Susanna Curtis, MD 203-200-4363 susanna.curtis@yale.edu

Locations
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United States, Connecticut
Yale New Haven Hospital Smilow Cancer Center Recruiting
New Haven, Connecticut, United States, 06510
Contact: Susanna Curtis, MD    203-200-4363    sussana.curtis@yale.edu   
Principal Investigator: Susanna Curtis, MD         
Sponsors and Collaborators
Yale University
Investigators
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Principal Investigator: Susanna Curtis, MD Yale University School of Medicine Oncology Section

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Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT03978156     History of Changes
Other Study ID Numbers: 2000021179
First Posted: June 6, 2019    Key Record Dates
Last Update Posted: July 29, 2019
Last Verified: July 2019

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