Cannabis-SCD: Vaporized Cannabis for Chronic Pain Associated With Sickle Cell Disease

Sponsor
University of California, San Francisco (Other)
Overall Status
Completed
CT.gov ID
NCT01771731
Collaborator
National Heart, Lung, and Blood Institute (NHLBI) (NIH), University of Minnesota (Other)
27
1
2
33.6
0.8

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
27 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Cannabinoid-Based Therapy and Approaches to Quantify Pain in Sickle Cell Disease
Study Start Date :
Aug 1, 2014
Actual Primary Completion Date :
May 12, 2017
Actual Study Completion Date :
May 19, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cannabis

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.

Drug: Cannabis
Other Names:
  • marijuana
  • Placebo Comparator: Placebo

    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.

    Drug: Cannabis
    Other Names:
  • marijuana
  • Outcome Measures

    Primary Outcome Measures

    1. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 San Francisco General Hospital San Francisco California United States 94110

    Sponsors and Collaborators

    • University of California, San Francisco
    • National Heart, Lung, and Blood Institute (NHLBI)
    • University of Minnesota

    Investigators

    • Principal Investigator: Donald I Abrams, MD, University of California, San Francisco

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    University of California, San Francisco
    ClinicalTrials.gov Identifier:
    NCT01771731
    Other Study ID Numbers:
    • U54HL117664-01
    • 6610
    First Posted:
    Jan 18, 2013
    Last Update Posted:
    Aug 18, 2020
    Last Verified:
    Aug 1, 2020
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Cannabis First, Then Placebo Placebo First, Then Cannabis
    Arm/Group Description This group received active THC:CBD cannabis during their first 5-day inpatient admission and placebo during the second admission. This group received placebo cannabis during their first 5-day inpatient admission and THC:CBD cannabis during the second.
    Period Title: Overall Study
    STARTED 13 14
    COMPLETED 11 12
    NOT COMPLETED 2 2

    Baseline Characteristics

    Arm/Group Title Cannabis First, Then Placebo Placebo First, Then Cannabis Total
    Arm/Group Description 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. 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. Total of all reporting groups
    Overall Participants 13 14 27
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    39.7
    (12.8)
    33.3
    (8.7)
    36.4
    (11.1)
    Sex: Female, Male (Count of Participants)
    Female
    7
    53.8%
    9
    64.3%
    16
    59.3%
    Male
    6
    46.2%
    5
    35.7%
    11
    40.7%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    13
    100%
    11
    78.6%
    24
    88.9%
    White
    0
    0%
    0
    0%
    0
    0%
    More than one race
    0
    0%
    3
    21.4%
    3
    11.1%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%

    Outcome Measures

    1. Primary Outcome
    Title Pain Rating Using Visual Analog Scale at Day 1 and Day 5
    Description 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

    Outcome Measure Data

    Analysis Population Description
    All participants received both interventions.
    Arm/Group Title Cannabis Placebo
    Arm/Group Description 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.
    Measure Participants 23 23
    Day 1
    40.5
    45.8
    Day 5
    30.3
    38.5

    Adverse Events

    Time Frame Adverse events were collected during the two 5-day admission periods separated by one month
    Adverse Event Reporting Description
    Arm/Group Title Cannabis Placebo
    Arm/Group Description 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.
    All Cause Mortality
    Cannabis Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/23 (0%) 0/23 (0%)
    Serious Adverse Events
    Cannabis Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/23 (0%) 0/23 (0%)
    Other (Not Including Serious) Adverse Events
    Cannabis Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 13/23 (56.5%) 12/23 (52.2%)
    Nervous system disorders
    Anxiety 9/23 (39.1%) 7/23 (30.4%)
    Sedation 13/23 (56.5%) 12/23 (52.2%)
    Disorientation 2/23 (8.7%) 3/23 (13%)
    Paranoia 1/23 (4.3%) 1/23 (4.3%)
    Confusion 2/23 (8.7%) 2/23 (8.7%)
    Dizziness 6/23 (26.1%) 3/23 (13%)
    Nausea 4/23 (17.4%) 6/23 (26.1%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Donald I. Abrams, MD
    Organization University of California San Francisco
    Phone 415-476-4082 ext 444
    Email Donald.Abrams@ucsf.edu
    Responsible Party:
    University of California, San Francisco
    ClinicalTrials.gov Identifier:
    NCT01771731
    Other Study ID Numbers:
    • U54HL117664-01
    • 6610
    First Posted:
    Jan 18, 2013
    Last Update Posted:
    Aug 18, 2020
    Last Verified:
    Aug 1, 2020