Sickle Cell Disease
Conditions
Brief summary
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
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.
Interventions
DRUGDronabinol
Dronabinol, an FDA approval oral agent containing synthetic tetrahydrocannabinol (THC)
DRUGPlacebo
placebo equivalent
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Icahn School of Medicine at Mount Sinai
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Dronabinol and placebo will be over-encapsulated so that neither participants nor investigators are aware of the subjects assignment.
Intervention model description
Participants will be randomized 1:1 to dronabinol or placebo.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patient Reported Measurement Outcome Information System (PROMIS) pain impact score | end of study at 8 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adult Sickle Cell Quality of Life Information System (ASCQ-Me) Pain impact | end of study at 8 weeks | Total scale from 20 to 80, median of 50 and SD of 10. Higher scores represent better health outcomes. |
| Quality of Life Outcomes | end of study at 8 weeks | 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. |
| WBC with differential | end of study at 8 weeks | 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. |
| C-reactive protein (CRP) | end of study at 8 weeks | 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. |
| substance P | end of study at 8 weeks | 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. |
| Vascular cell adhesion protein 1 (VCAM-1) | end of study at 8 weeks | marker of Inflammation. plasma levels of oxidative stress and adhesion molecules |
| cytokine IL1a | end of study at 8 weeks | 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. |
| cytokine IL1b | end of study at 8 weeks | 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. |
| cytokine IL6 | end of study at 8 weeks | marker of Inflammation. Interleukin-6 (IL-6) is a pleiotropic cytokine with central roles in immune regulation, inflammation, hematopoiesis, and oncogenesis. |
| tryptase | end of study at 8 weeks | marker of Inflammation. tryptase is an enzyme found in mast cells |
| cytokine IL10 | end of study at 8 weeks | marker of Inflammation. Interleukin 10 (IL-10), also known as human cytokine synthesis inhibitory factor (CSIF), is an anti-inflammatory cytokine. |
| tumor necrosis factor alpha (TNFα). | end of study at 8 weeks | 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. |
| PROMIS domains | end of study at 8 weeks | 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. |
| Columbia suicide severity rating scale | end of study at 8 weeks | Columbia suicide severity rating scale. Full range from 0 to 9. Higher score represents higher intensity suicidal ideation. |
| Prodromal questionnaire brief version (PQ-B) | end of study at 8 weeks | Prodromal questionnaire brief version: 21-item self-report instrument. Full scale range from 0 to 21, higher score represents poorer health outcomes |
| PROMIS domain for neuropathic pain quality | end of study at 8 weeks | Total scale from 20-80, median of 50 and SD of 10. Higher scores represent worse outcomes. |
| PROMIS domain for nociceptive pain quality | end of study at 8 weeks | Total scale from 20-80, median of 50 and SD of 10. Higher scores represent worse outcomes. |
| The Leeds assessment of neuropathic symptoms and signs (LANSS) Pain Scale | end of study at 8 weeks | 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. |
| cytokine IL4 | end of study at 8 weeks | 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. |
Countries
United States
Contacts
Primary ContactSusanna Curtis, MD, PhD
Outcome results
None listed