Sickle Cell Disease
Conditions
Keywords
chronic pain, epidiolex, cannabidiol
Brief summary
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.
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.
Interventions
DRUGCannabidiol
Cannabidiol (CBD) twice daily taken orally for 4-weeks
DRUGPlacebo
Placebo equivalent twice daily taken orally for 4-weeks
Sponsors
Icahn School of Medicine at Mount Sinai
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Twice daily cannabidiol given at 3 dose levels, 200mg, 400mg, and 600mg, for 4 weeks, with 1:1:1:1 allocation of placebo to 3 drug doses.
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 * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Necrosis Factor-alpha level | at 4 weeks | Plasma levels of tumor necrosis factor-alpha, a marker of inflammation in sickle cell disease will be collected. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Levels of Markers of Inflammation | at 4 weeks | Levels of inflammatory markers (IL1a, IL1b, IL6, IL4 and IL10) will be collected. |
| White Blood Cell with differential | at 4 weeks | 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. |
| C-reactive protein level | at 4 weeks | 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. |
| Substance P levels | at 4 weeks | 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. |
| Cytokines levels | at 4 weeks | 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. |
| Adult Sickle Cell Quality of Life Measurement System | at 4 weeks | 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. |
| Patient Reported Outcome Information System (PROMIS) to measure Pain | at 4 weeks | 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) |
| Tryptase levels | at 4 weeks | 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. |
| Patient Reported Outcomes Measurement Information System (PROMIS) | at 4 weeks | 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. |
| Oral Morphine Equivalents (OME) | at 4 weeks | Oral Morphine Equivalents (OME) |
| Number of Emergency Room Visits | at 4 weeks | Number of emergency room visits |
| Number of Hospital Admissions | at 4 weeks | Number of hospital admissions |
| Number of Psychiatric Facility Utilizations | at 4 weeks | Number of psychiatric facility utilization |
| Columbia-Suicide Severity Rating Scale - Severity and Intensity Subscale (C-SSRS SI) | at 4 weeks | 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. |
| Prodromal Questionnaire - Brief Version (PQ-B) | at 4 weeks | 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 |
| Leeds Assessment of Neuropathic Symptoms and Signs pain scale (S-LANSS) | 4 weeks | 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. |
Countries
United States
Contacts
Primary ContactSusanna Curtis
Outcome results
None listed