Cannabinoids for the Reduction of Inflammation and Sickle Cell Related Pain (CRISP)

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

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).

Study Overview

• Status: Recruiting
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: Placebo; Drug: Dronabinol

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Susanna Curtis, MD, PhD; Phone Number: 2036718154; Email: susanna.curtis@mssm.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Mount Sinai Hospital
      • Contact: Susanna Curtis, MD, PhD; Email: susanna.curtis@mssm.edu
      • Principal Investigator: Susanna Curtis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dronabinol; 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; Dronabinol, an FDA approval oral agent containing synthetic tetrahydrocannabinol (THC); Other Names: Marinol
Placebo Comparator: Placebo; A placebo comparator	Drug: Placebo; placebo equivalent

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Susanna Curtis, Mount Sinai Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: August 25, 2022
• First Submitted That Met QC Criteria: August 25, 2022
• First Posted (Actual): August 29, 2022

Study Record Updates

• Last Update Posted (Estimated): October 2, 2025
• Last Update Submitted That Met QC Criteria: September 29, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell; Organic Chemicals; Hydrocarbons; Terpenes; Cannabinoids; Dronabinol
• Other Study ID Numbers: GCO 22-1141; K23HL151884 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
• IPD Sharing Time Frame: Specify Other Time FrameOn request.

IPD Sharing Access Criteria

Investigators whose proposed use of the data has been approved by an independent review committee ('learned intermediary') identified for this purpose.

Any purpose. Proposals should be directed to susanna.curtis@mssm.edu. To gain access, data requestors will need to sign a data access agreement. Data are available for 5 years at a third party website (website tbd.)

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

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.: No