Vaporized Cannabis for Chronic Pain Associated With Sickle Cell Disease

NCT ID: NCT01771731

Last Updated: 2020-08-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-08-31
• Study Completion Date: 2017-05-19

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.

Conditions

Sickle Cell Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Cannabis

Intervention Type: DRUG

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.

Group Type: PLACEBO_COMPARATOR

Cannabis

Intervention Type: DRUG

Interventions

Cannabis

Intervention Type: DRUG

Other Intervention Names

marijuana

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of Minnesota

OTHER

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Donald I Abrams, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

San Francisco General Hospital

San Francisco, California, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 32678452 (View on PubMed)

Oniyangi O, Cohall DH. Phytomedicines (medicines derived from plants) for sickle cell disease. Cochrane Database Syst Rev. 2020 Sep 25;9(9):CD004448. doi: 10.1002/14651858.CD004448.pub7.

Reference Type: DERIVED

PMID: 32977351 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

6610

Identifier Type: OTHER

Identifier Source: secondary_id

U54HL117664-01

Identifier Type: -

Identifier Source: org_study_id