Cannabidiol in Sickle Cell Disease (SPICE)

Treatment of Sickle Cell Pain and Inflammation With Cannabidiol (SPICe)

Randomized, placebo-controlled, double masked, dose finding study of twice daily cannabidiol given at 3 dose levels, 200mg, 400mg, and 600mg, compared to placebo for 4 weeks.

Study Overview

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

Detailed Description

The researchers will conduct a randomized, double blind, placebo-controlled, study of cannabidiol in an oral formulation. Participants will be enrolled when they are not in pain crisis and have demonstrated a urine toxicology test free from cannabinoids in the past 30 days. The sample size will be 52 participants, aged ≥18, with 1:1:1:1 allocation of placebo to 3 drug doses. This is a dose finding study with a primary outcome of reduction of inflammatory cytokine TNFα.

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Susanna Curtis; Phone Number: 212-241-3650; Email: susanna.curtis@mssm.edu

Study Locations

• United States
  • New York
    • Manhattan, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai
      • Contact: Susanna Curtis, MD, PhD; Email: susanna.curtis@mssm.edu
      • Principal Investigator: Susanna Curtis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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
• Willing to abstain from cannabis, medical and illicit, during study weeks 1 through 4 • 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

Exclusion Criteria:

• No known intolerance to cannabinoids
• No history of psychotic episode, psychosis, or active suicidality
• No contraindication to epidiolex with attention to potential side effects, concurrent medications/substances, and concurrent medical problems, as evaluated by a physician
• Not a daily cannabis user
• No diagnosis of active substance use disorder
• No ALT>3 times the upper limit of normal

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Twice daily matching placebo	Drug: Placebo; Placebo equivalent twice daily taken orally for 4-weeks
Active Comparator: Cannabidiol 200 mg; Twice daily 200 mg cannabidiol	Drug: Cannabidiol; Cannabidiol (CBD) twice daily taken orally for 4-weeks; Other Names: Epidiolex
Active Comparator: Cannabidiol 400 mg; Twice daily 400 mg cannabidiol	Drug: Cannabidiol; Cannabidiol (CBD) twice daily taken orally for 4-weeks; Other Names: Epidiolex
Active Comparator: Cannabidiol 600 mg; Twice daily 600 mg cannabidiol	Drug: Cannabidiol; Cannabidiol (CBD) twice daily taken orally for 4-weeks; Other Names: Epidiolex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor Necrosis Factor-alpha level	Plasma levels of tumor necrosis factor-alpha, a marker of inflammation in sickle cell disease will be collected.	at 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of Markers of Inflammation	Levels of inflammatory markers (IL1a, IL1b, IL6, IL4 and IL10) will be collected.	at 4 weeks
White Blood Cell with differential	The blood differential test measures the percentage of each type of white blood cell (WBC) that are in the blood. This test is done to diagnose an infection, anemia, or leukemia. It may also be used to monitor a condition or to see if treatment is working.	at 4 weeks
C-reactive protein level	C-reactive protein (CRP) is produced by the liver. The CRP test is a general test to check for inflammation in the body. It is not a specific test. This means it can reveal that inflammation is present somewhere in the body, but it cannot pinpoint the exact location or reason.	at 4 weeks
Tryptase levels	Tryptase is enzyme released by mast cells in the body during allergic reactions and other immune responses. Elevated levels in the blood can indicate severe allergic reactions (like anaphylaxis), mast cell disorders, or certain inflammatory conditions.	at 4 weeks
Substance P levels	Substance P is neuropeptide that functions as a neurotransmitter and acts as a key mediator of pain sensation and inflammation in the body. It plays a role in various physiological processes including stress responses, mood regulation, and neurogenic inflammation.	at 4 weeks
Cytokines levels	Cytokines is a protein measured in blood samples to assess the body's immune and inflammatory responses to treatment. Elevated or reduced levels can indicate how the immune system is reacting and may help determine treatment effectiveness or disease progression.	at 4 weeks
Adult Sickle Cell Quality of Life Measurement System	The ASCQ-Me pain scale ranges from 0-100, with a standardized sickle cell disease population mean of 50 (standard deviation=10), where lower scores signify worse disease impact.	at 4 weeks
Patient Reported Outcome Information System (PROMIS) to measure Pain	Patient Reported Outcome Information System (PROMIS) domains for pain impact, neuropathic pain, and nociceptive pain: A standardized patient-reported measure assessing different aspects of pain experience. The measure includes subscales for pain impact (0-40), neuropathic pain (0-30), and nociceptive pain (0-30), each evaluating distinct pain mechanisms and experiences. Total score ranges from 0-100, with higher scores indicating greater pain severity and impact on daily functioning. Results are reported as T-scores (population mean=50, standard deviation=10)	at 4 weeks
Leeds Assessment of Neuropathic Symptoms and Signs pain scale (S-LANSS)	Leeds assessment of neuropathic signs and symptoms The S-LANSS is a self-reported version of the Leeds Assessment of Neuropathic Symptoms and Signs pain scale. It aims to differentiate neuropathic pain (pain from nerve damage) from somatic or nociceptive pain (pain from body damage). Scores range from 0-24, with higher scores indicating greater pain.	4 weeks
Patient Reported Outcomes Measurement Information System (PROMIS)	The PROMIS (Patient-Reported Outcomes Measurement Information System) for domains: Anxiety, Appetite, Nausea, and Cognitive function. The PROMIS measure is a brief, computer-adapted measure of symptoms for the domains. Each is a normalized measure with a mean of 50 and standard deviation of 10. Higher scores represent increased symptoms.	at 4 weeks
Oral Morphine Equivalents (OME)	Oral Morphine Equivalents (OME)	at 4 weeks
Number of Emergency Room Visits	Number of emergency room visits	at 4 weeks
Number of Hospital Admissions	Number of hospital admissions	at 4 weeks
Number of Psychiatric Facility Utilizations	Number of psychiatric facility utilization	at 4 weeks
Columbia-Suicide Severity Rating Scale - Severity and Intensity Subscale (C-SSRS SI)	The C-SSRS rates an individual's degree of suicidal ideation (SI) on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent." The subscale identifies SI severity and intensity, which may be indicative of an individual's intent to commit suicide. C-SSRS SI ranges from 0 (no SI) to 5 (active SI with plan and intent). Higher score indicates more severity.	at 4 weeks
Prodromal Questionnaire - Brief Version (PQ-B)	The Prodromal Questionnaire Brief Version (PQ-B) is a patient questionnaire that assesses the existence of a prodromal state or fully developed psychosis. The PQ-B includes 21 items that refer to thoughts, feelings and experiences that describe various symptoms, including abnormal perception, unconventional thinking, paranoia and negative symptoms. For each item, the participant is asked to indicate whether they had experienced that phenomenon in the past month (yes/no). The total score is calculated by summing the number of "yes" responses across all items. Full range is 0-21, with higher scores indicating a greater likelihood of experiencing prodromal symptoms or fully developed psychosis	at 4 weeks

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Investigators: Principal Investigator: Susanna Curtis, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: April 9, 2025
• First Submitted That Met QC Criteria: April 9, 2025
• First Posted (Actual): April 16, 2025

Study Record Updates

• Last Update Posted (Estimated): June 25, 2025
• Last Update Submitted That Met QC Criteria: June 24, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: chronic pain; cannabidiol; epidiolex
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Anemia, Sickle Cell; Anticonvulsants; Cannabidiol
• Other Study ID Numbers: STUDY-24-00903; IN123001222 (Other Grant/Funding Number: American Society of Hematology)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All of the individual participant data collected during the trial, after deidentification.
• IPD Sharing Time Frame: Specify Other Time FrameOn request.
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal. 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 (Link TBD).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; 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