Cannabinoids for the Reduction of Inflammation and Sickle Cell Related Pain

Study Overview
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Brief Summary
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A randomized, double blind, 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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A randomized, double blind, study of dronabinol as a palliative agent in the treatment of pain, inflammation, and other complications of sickle cell disease (SCD). Primary Objective: To determine whether dronabinol will improve pain and QOL in adults with SCD and chronic pain. Secondary Objectives: To assess dronabinol's effect on markers of inflammation in patients with SCD compared to placebo. To determine the safety and tolerability of dronabinol use in adults with SCD compared to placebo.

Official Title
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Dronabinol for the Reduction of Chronic Pain and Inflammation in People With Sickle Cell Disease

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Drug: Dronabinol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Age >18 years 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 If on a SCD modifying therapy (hydroxyurea, regular blood transfusions, L-glutamine, voxelotor, crizanlizumab), on stable dose for at least 3 months If using opioids for pain at home, on stable dose for at least 3 months One urine toxicology negative for cannabinoids within 30 days of randomization No known intolerance to dronabinol, or marijuana No history of psychotic episode, psychosis, or active suicidality No contraindication to dronabinol with attention to potential side effects, concurrent medications/substances, and concurrent medical problems, as evaluated by a physician Willing to abstain from cannabis, medical and illicit, during study weeks 1 through 8 Not pregnant or nursing If a woman capable of becoming pregnant, willing to use a medically accepted form of birth control for the duration of study participation. Accepted forms include oral contraception, medroxyprogesterone, contraceptive implants or patch, surgical sterilization, total abstinence. Able to consent for research No daily cannabis use No diagnosis of active substance use disorder

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomized 1:1 to dronabinol or placebo.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dronabinol<br>BID for 8 weeks. Dosage will be individualized per patient. In days 1-4 of the study each patient will be titrated from 5mg bid to a minimum dose of 2.5 mg bid to a maximum dose of 10 mg bid depending on patient preference. | Drug: Dronabinol<br>* Dronabinol, an FDA approval oral agent containing synthetic tetrahydrocannabinol (THC)<br>* Other names: Marinol;|
| Placebo Comparator: Placebo<br>A placebo comparator | Drug: Placebo<br>* placebo equivalent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Reported Measurement Outcome Information System (PROMIS) pain impact score | Change in Patient Reported Measurement Outcome Information System (PROMIS) pain impact score. Total scale from 20-80, median of 50 and SD of 10. Higher score represent poorer health outcomes. | end of study at 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adult Sickle Cell Quality of Life Information System (ASCQ-Me) Pain impact | Total scale from 20 to 80, median of 50 and SD of 10. Higher scores represent better health outcomes. | end of study at 8 weeks | 
| Quality of Life Outcomes | ASCQ-Me survey domains for emotional impact, social impact, stiffness, and sleep. Each domain scale from 20 to 80, median of 50 and SD of 10. Higher scores represent better health outcomes. Total scale from 20 to 80, median of 50 and SD of 10. Higher scores represent better health outcomes. | end of study at 8 weeks | 
| WBC with differential | a marker of Inflammation. The blood differential test measures the percentage of each type of white blood cell (WBC) in the blood. It also reveals if there are any abnormal or immature cells. | end of study at 8 weeks | 
| C-reactive protein (CRP) | marker of Inflammation. C-reactive protein (CRP) is produced by the liver. The level of CRP rises when there is inflammation throughout the body. It is one of a group of proteins, called acute phase reactants, that go up in response to inflammation. The levels of acute phase reactants increase in response to certain inflammatory proteins called cytokines. These proteins are produced by white blood cells during inflammation. | end of study at 8 weeks | 
| tryptase | marker of Inflammation. tryptase is an enzyme found in mast cells | end of study at 8 weeks | 
| substance P | marker of Inflammation. Substance P (P standing for Preparation or Powder) is a neuropeptide - but only nominally so, as it is ubiquitous. Its receptor - the neurokinin type 1 - is distributed over cytoplasmic membranes of many cell types (neurons, glia, endothelia of capillaries and lymphatics, fibroblasts, stem cells, white blood cells) in many tissues and organs. SP amplifies or excites most cellular processes. | end of study at 8 weeks | 
| Vascular cell adhesion protein 1 (VCAM-1) | marker of Inflammation. plasma levels of oxidative stress and adhesion molecules | end of study at 8 weeks | 
| cytokine IL1a | marker of Inflammation. Interleukin 1 alpha (IL-1α) also known as hematopoietin 1 is a cytokine of the interleukin 1 family that in humans is encoded by the IL1A gene. | end of study at 8 weeks | 
| cytokine IL1b | marker of Inflammation. Interleukin 1 beta (IL-1β) also known as leukocytic pyrogen, leukocytic endogenous mediator, mononuclear cell factor, lymphocyte activating factor and other names, is a cytokine protein that in humans is encoded by the IL1B gene. | end of study at 8 weeks | 
| cytokine IL6 | marker of Inflammation. Interleukin-6 (IL-6) is a pleiotropic cytokine with central roles in immune regulation, inflammation, hematopoiesis, and oncogenesis. | end of study at 8 weeks | 
| cytokine IL4 | marker of Inflammation. The interleukin 4 (IL4, IL-4) is a cytokine that induces differentiation of naive helper T cells (Th0 cells) to Th2 cells. | end of study at 8 weeks | 
| cytokine IL10 | marker of Inflammation. Interleukin 10 (IL-10), also known as human cytokine synthesis inhibitory factor (CSIF), is an anti-inflammatory cytokine. | end of study at 8 weeks | 
| tumor necrosis factor alpha (TNFα). | marker of Inflammation. Tumor necrosis factor (TNF), a 17 kDa protein consisting of 157 amino acids, is a homotrimer in solution that is mainly produced by activated macrophages, T lymphocytes, and natural killer (NK) cells. | end of study at 8 weeks | 
| PROMIS domains | PROMIS domains for anxiety, appetite, nausea, and cognitive function, opioid use in oral morphine equivalents (OME), episodes of emergency room, hospital, or psychiatric facility utilization. Each domain scale from 20 to 80, median of 50 and SD of 10. Higher scores represent better health outcomes. Total scale from 20 to 80, median of 50 and SD of 10. Higher scores represent better health outcomes. | end of study at 8 weeks | 
| Columbia suicide severity rating scale | Columbia suicide severity rating scale. Full range from 0 to 9. Higher score represents higher intensity suicidal ideation. | end of study at 8 weeks | 
| Prodromal questionnaire brief version (PQ-B) | Prodromal questionnaire brief version: 21-item self-report instrument. Full scale range from 0 to 21, higher score represents poorer health outcomes | end of study at 8 weeks | 
| PROMIS domain for neuropathic pain quality | Total scale from 20-80, median of 50 and SD of 10. Higher scores represent worse outcomes. | end of study at 8 weeks | 
| PROMIS domain for nociceptive pain quality | Total scale from 20-80, median of 50 and SD of 10. Higher scores represent worse outcomes. | end of study at 8 weeks | 
| The Leeds assessment of neuropathic symptoms and signs (LANSS) Pain Scale | The Leeds assessment of neuropathic symptoms and signs (LANSS) Pain Scale comprises of a 7-item pain scale, including the sensory descriptors and items for sensory examination. Out of the seven items in the Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale (LANSS), five are symptom related and two are examination items. Full scale from scores between 0 and 24, higher score represents poorer health outcomes. | end of study at 8 weeks |