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

• ClinicalTrials.gov Identifier: NCT01771731
• Recruitment Status: Completed
• First Posted: January 18, 2013
• Results First Posted: August 18, 2020
• Last Update Posted: August 18, 2020
• Sponsor: University of California, San Francisco
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); University of Minnesota
• Information provided by (Responsible Party): University of California, San Francisco

Tracking Information

• First Submitted Date: January 14, 2013
• First Posted Date: January 18, 2013
• Results First Submitted Date: September 3, 2019
• Results First Posted Date: August 18, 2020
• Last Update Posted Date: August 18, 2020
• Study Start Date: August 2014
• Actual Primary Completion Date: May 12, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 5, 2020)

Pain Rating Using Visual Analog Scale at Day 1 and Day 5 [ Time Frame: 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.

Original Primary Outcome Measures (submitted: January 16, 2013)

pain level [ Time Frame: Days 1 and 5 of two 5-day study periods ]

Subjects will complete a 5-day pain diary prior to admission to the Clinical Research Center (CRC) to establish a baseline of pain. They will then be assigned to inhale either vaporized cannabis of mixed THC/CBD content (4.7% THC/5.1% CBD) or placebo cannabis (0% THC/0% CBD). Participants and personnel will be blinded as to assignment. Pain will be evaluated during the 5-day inpatient exposure. Participants will be asked to participate in two such 5-day sessions separated by at least a 2-week washout so that each will be exposed to the two experimental conditions.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Vaporized Cannabis for Chronic Pain Associated With Sickle Cell Disease
• Official Title: Cannabinoid-Based Therapy and Approaches to Quantify Pain in Sickle Cell Disease

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.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Sickle Cell Disease

Intervention

Drug: Cannabis

Other Name: marijuana

Study Arms

• 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.
  Intervention: Drug: Cannabis
• 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.
  Intervention: Drug: Cannabis

Publications *

• Abrams DI, Couey P, Dixit N, Sagi V, Hagar W, Vichinsky E, Kelly ME, Connett JE, Gupta K. Effect of Inhaled Cannabis for Pain in Adults With Sickle Cell Disease: A Randomized Clinical Trial. JAMA Netw Open. 2020 Jul 1;3(7):e2010874. doi: 10.1001/jamanetworkopen.2020.10874.
• Oniyangi O, Cohall DH. Phytomedicines (medicines derived from plants) for sickle cell disease. Cochrane Database Syst Rev. 2020 Sep 25;9:CD004448. doi: 10.1002/14651858.CD004448.pub7.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 5, 2020): 27
• Original Estimated Enrollment (submitted: January 16, 2013): 35
• Actual Study Completion Date: May 19, 2017
• Actual Primary Completion Date: May 12, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01771731
• Other Study ID Numbers: U54HL117664-01; 6610 ( Other Identifier: UCSF Clinical and Translational Science Institute )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: University of California, San Francisco
• Study Sponsor: University of California, San Francisco

Collaborators

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

Investigators

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

• PRS Account: University of California, San Francisco
• Verification Date: August 2020