Sickle Cell Disease
Conditions
Brief summary
Our primary objective is to assess whether inhaling vaporized cannabis ameliorates chronic pain in patients with sickle cell disease (SCD). As these patients will all be on chronic opioid analgesics, the investigators will also assess the possible synergistic affect between inhaled cannabis and opioids. The investigators will also assess the clinical safety of the concomitant use of cannabinoids and these opioids in patients with SCD by monitoring the short-term side effects associated with combined therapy. Finally, the investigators will evaluate the short-term effects of inhaled cannabis on markers of inflammation and disease progression in patients with SCD. Hypotheses are as follows: 1. Inhaled cannabis will significantly reduce chronic pain in patients with SCD. 2. Inhaled cannabis will significantly alter the short-term side effects experienced by patients who take opioids for SCD. 3. Inhaled cannabis will significantly alter markers of inflammation and disease progression in patients with SCD compared to placebo.
Detailed description
This is a proof-of-principle investigation of the safety and potential effectiveness of inhaled vaporized cannabis when added to a stable analgesic regimen in sickle cell disease (SCD) patients with chronic pain. The study will be comprised of two 5-day intervention periods in the inpatient setting (the Clinical Research Center at SFGH), with completion of a 5-day daily pain diary prior to admission to establish an outpatient baseline. Participants will be randomly assigned, in double-blind fashion, to treatment with (A) vaporized cannabis with an approximately 1:1 ration of delta-9-tetrahydrocannabinol:cannabidiol or (B) vaporized placebo. Those who receive treatment A during the first admission will receive treatment B in the second, and those who receive treatment B during the first admission will receive treatment A in the second. The two admissions will be spaced at least 14 days apart. On Day 1 of each admission, subjects will provide blood samples for baseline markers of inflammation and SCD disease progression. They will undergo assessments of pain, mood, and quality of life. At 12 pm on Day 1, they will inhale vaporized study agent (equivalent to 1 cannabis/placebo cigarette) using the Volcano® vaporizer; on Days 2-4 they will inhale study agent at 8 am, 2 pm, and 8 pm, and they will inhale their final dose on Day 5 at 8 am. Subjects will continue their pre-study analgesic regimen while in the study. If additional analgesia is required, supplemental therapy will be administered and the dose recorded. Pain measurements by visual analogue scale will be obtained every 2 hours while subjects are awake. On Day 5 a second set of blood samples for inflammation markers and disease progression will be obtained, and subjects will again complete pain, mood, and quality of life assessments.
Interventions
DRUGCannabis
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
University of Minnesota
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Sickle cell disease, including sickle cell anemia (SS), sickle-hemoglobin C disease (SC), and sickle beta thalassemia disease (Sb). * Ongoing opioid analgesic therapy for chronic sickle cell disease-associated pain. * Subjects must be on a stable dose of analgesic medication (opioid or other) for at least 2 weeks before enrollment. * All men and women in this study must agree to use adequate birth control during this study. Acceptable barrier birth control methods are a male condom, female condom, diaphragm, or intra-uterine (IUD). * All women of reproductive potential (who have not reached menopause or undergone hysterectomy, oophorectomy, or tubal ligation) must have a negative urine b-HCG pregnancy test performed before initiating the protocol-specified medication. * Prior history of use of cannabis. Subjects must have smoked cannabis on at least 6 occasions in their lifetime prior to enrollment. * Subjects will self-report abstaining from smoking or ingesting cannabis for one week prior to their enrollment into the study. * Able to understand and follow the instructions of the investigator, including completing the pain intensity rating scales. * Karnofsky Performance Scale \>60. * Able and willing to provide informed consent. * Able and willing to spend two separate periods of 5 days and 4 nights in the Clinical Research Center at SFGH.
Exclusion criteria
* Severe coronary artery disease, uncontrolled hypertension, cardiac ventricular conduction abnormalities, orthostatic mean blood pressure drop greater than 24 mmHg, severe chronic obstructive pulmonary disease. * Evidence of clinically significant hepatic or renal dysfunction based on judgment of physician. * Positive serum THC level on Day 1 of study. * Active substance abuse (e.g., alcohol or injection drugs) as determined by urine toxicity screening. * Neurologic dysfunction or psychiatric disorder severe enough to interfere with assessment of pain or sensory systems. * Current use of smoked tobacco products. * Women who are pregnant or breast-feeding may not take part in this study. * Unable to read or speak English.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Rating Using Visual Analog Scale at Day 1 and Day 5 | Day 1 and Day 5 | Visual analog scale (VAS) used to assess pain. The scale range is 0-100, lower score means lower pain, higher score means higher pain. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cannabis First, Then Placebo Contents of 1 cannabis cigarette (4.7% THC/5.1% CBD) will be vaporized and inhaled at 12pm on Day 1; 8am, 2pm and 8pm on Days 2-4; and 8am on Day 5.
Contents of 1 placebo cigarette (0% THC/0% CBD) will be vaporized and inhaled at 12pm on Day 1; 8am, 2pm and 8pm on Days 2-4; and 8am on Day 5. | 13 |
| Placebo First, Then Cannabis Contents of 1 placebo cigarette (0% THC/0% CBD) will be vaporized and inhaled at 12pm on Day 1; 8am, 2pm and 8pm on Days 2-4; and 8am on Day 5.
Contents of 1 cannabis cigarette (4.7% THC/5.1% CBD) will be vaporized and inhaled at 12pm on Day 1; 8am, 2pm and 8pm on Days 2-4; and 8am on Day 5. | 14 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse event: Pain Crisis | 1 | 1 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo First, Then Cannabis | Total | Cannabis First, Then Placebo |
|---|---|---|---|
| Age, Continuous | 33.3 years STANDARD_DEVIATION 8.7 | 36.4 years STANDARD_DEVIATION 11.1 | 39.7 years STANDARD_DEVIATION 12.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 24 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 9 Participants | 16 Participants | 7 Participants |
| Sex: Female, Male Male | 5 Participants | 11 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 23 |
| other Total, other adverse events | 13 / 23 | 12 / 23 |
| serious Total, serious adverse events | 0 / 23 | 0 / 23 |
Outcome results
Primary
Pain Rating Using Visual Analog Scale at Day 1 and Day 5
Visual analog scale (VAS) used to assess pain. The scale range is 0-100, lower score means lower pain, higher score means higher pain.
Time frame: Day 1 and Day 5
Population: All participants received both interventions.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Cannabis | Pain Rating Using Visual Analog Scale at Day 1 and Day 5 | Day 1 | 40.5 score on a scale |
| Cannabis | Pain Rating Using Visual Analog Scale at Day 1 and Day 5 | Day 5 | 30.3 score on a scale |
| Placebo | Pain Rating Using Visual Analog Scale at Day 1 and Day 5 | Day 1 | 45.8 score on a scale |
| Placebo | Pain Rating Using Visual Analog Scale at Day 1 and Day 5 | Day 5 | 38.5 score on a scale |