Back to resultsCannabinoids for the Reduction of Inflammation and Sickle Cell Related Pain (CRISP)
Primary Purpose
Sickle Cell Disease
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Dronabinol
Placebo
Sponsored by
About this trial
This is an interventional supportive care trial for Sickle Cell Disease
Eligibility 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
Sites / Locations
- Mount Sinai HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Dronabinol
Placebo
Arm Description
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.
A placebo comparator
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
tryptase
marker of Inflammation. tryptase is an enzyme found in mast cells
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.
Vascular cell adhesion protein 1 (VCAM-1)
marker of Inflammation. plasma levels of oxidative stress and adhesion molecules
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.
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.
cytokine IL6
marker of Inflammation. Interleukin-6 (IL-6) is a pleiotropic cytokine with central roles in immune regulation, inflammation, hematopoiesis, and oncogenesis.
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.
cytokine IL10
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).
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
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
Columbia suicide severity rating scale. Full range from 0 to 9. Higher score represents higher intensity suicidal ideation.
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
PROMIS domain for neuropathic pain quality
Total scale from 20-80, median of 50 and SD of 10. Higher scores represent worse outcomes.
PROMIS domain for nociceptive pain quality
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
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.
Full Information
NCT ID
NCT05519111
First Posted
August 25, 2022
Last Updated
June 12, 2023
Sponsor
Icahn School of Medicine at Mount Sinai
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
1. Study Identification
Unique Protocol Identification Number
NCT05519111
Brief Title
Cannabinoids for the Reduction of Inflammation and Sickle Cell Related Pain
Acronym
CRISP
Official Title
Dronabinol for the Reduction of Chronic Pain and Inflammation in People With Sickle Cell Disease
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 1, 2022 (Actual)
Primary Completion Date
October 30, 2025 (Anticipated)
Study Completion Date
October 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Icahn School of Medicine at Mount Sinai
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
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.
No
Data Monitoring Committee
Yes
5. Study Description
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.
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
Supportive Care
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Participants will be randomized 1:1 to dronabinol or placebo.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Dronabinol and placebo will be over-encapsulated so that neither participants nor investigators are aware of the subjects assignment.
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dronabinol
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
A placebo comparator
Intervention Type
Drug
Intervention Name(s)
Dronabinol
Other Intervention Name(s)
Marinol
Intervention Description
Dronabinol, an FDA approval oral agent containing synthetic tetrahydrocannabinol (THC)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
placebo equivalent
Primary Outcome Measure Information:
Title
Patient Reported Measurement Outcome Information System (PROMIS) pain impact score
Description
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.
Time Frame
end of study at 8 weeks
Secondary Outcome Measure Information:
Title
Adult Sickle Cell Quality of Life Information System (ASCQ-Me) Pain impact
Description
Total scale from 20 to 80, median of 50 and SD of 10. Higher scores represent better health outcomes.
Time Frame
end of study at 8 weeks
Title
Quality of Life Outcomes
Description
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.
Time Frame
end of study at 8 weeks
Title
WBC with differential
Description
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.
Time Frame
end of study at 8 weeks
Title
C-reactive protein (CRP)
Description
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.
Time Frame
end of study at 8 weeks
Title
tryptase
Description
marker of Inflammation. tryptase is an enzyme found in mast cells
Time Frame
end of study at 8 weeks
Title
substance P
Description
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.
Time Frame
end of study at 8 weeks
Title
Vascular cell adhesion protein 1 (VCAM-1)
Description
marker of Inflammation. plasma levels of oxidative stress and adhesion molecules
Time Frame
end of study at 8 weeks
Title
cytokine IL1a
Description
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.
Time Frame
end of study at 8 weeks
Title
cytokine IL1b
Description
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.
Time Frame
end of study at 8 weeks
Title
cytokine IL6
Description
marker of Inflammation. Interleukin-6 (IL-6) is a pleiotropic cytokine with central roles in immune regulation, inflammation, hematopoiesis, and oncogenesis.
Time Frame
end of study at 8 weeks
Title
cytokine IL4
Description
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.
Time Frame
end of study at 8 weeks
Title
cytokine IL10
Description
marker of Inflammation. Interleukin 10 (IL-10), also known as human cytokine synthesis inhibitory factor (CSIF), is an anti-inflammatory cytokine.
Time Frame
end of study at 8 weeks
Title
tumor necrosis factor alpha (TNFα).
Description
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.
Time Frame
end of study at 8 weeks
Title
PROMIS domains
Description
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.
Time Frame
end of study at 8 weeks
Title
Columbia suicide severity rating scale
Description
Columbia suicide severity rating scale. Full range from 0 to 9. Higher score represents higher intensity suicidal ideation.
Time Frame
end of study at 8 weeks
Title
Prodromal questionnaire brief version (PQ-B)
Description
Prodromal questionnaire brief version: 21-item self-report instrument. Full scale range from 0 to 21, higher score represents poorer health outcomes
Time Frame
end of study at 8 weeks
Title
PROMIS domain for neuropathic pain quality
Description
Total scale from 20-80, median of 50 and SD of 10. Higher scores represent worse outcomes.
Time Frame
end of study at 8 weeks
Title
PROMIS domain for nociceptive pain quality
Description
Total scale from 20-80, median of 50 and SD of 10. Higher scores represent worse outcomes.
Time Frame
end of study at 8 weeks
Title
The Leeds assessment of neuropathic symptoms and signs (LANSS) Pain Scale
Description
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.
Time Frame
end of study at 8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Susanna Curtis, MD, PhD
Phone
2036718154
Email
susanna.curtis@mssm.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Susanna Curtis
Organizational Affiliation
MOUNT SINAI HOSPITAL
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mount Sinai Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Susanna Curtis, MD, PhD
Email
susanna.curtis@mssm.edu
First Name & Middle Initial & Last Name & Degree
Susanna Curtis
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.)
Learn more about this trial
Cannabinoids for the Reduction of Inflammation and Sickle Cell Related Pain
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