Assessing the Safety of Buprenorphine in People With Sickle Cell Disease

This study will assess the safety of changing pain medications (opioids) adult sickle cell patients take to another type of medication therapy (buprenorphine). Patients will be asked questions about their quality of life. Other tools for assessment will also be administered.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: buprenorphine

Detailed Description

This is a descriptive, pilot study to assess the safety of converting a subset of adult sickle cell patients who are on effective disease modifying therapy (on high dose oral opioids who are unable to wean off opioids) and who continue to have frequent acute visits where parenteral opioids are administered to convert all opioid treatments to buprenorphine. Quality of life will be assessed using the Adult Sickle Cell Quality of life Measurement tool (ASCQ-Me), the Brief Pain Inventory (BPI), two Patient-Reported Outcomes Measurement Information System (PROMIS) surveys (short-form Pain Interference and Physical Function), and frequency of acute pain visits.

Buprenorphine is a partial mu-agonist and kappa antagonist and has a high affinity for the mu receptors with an elimination half-life of 28-37 hours for the sublingual administration. The lower risk for misuse, diminished withdrawal symptoms and cravings for opioids as well as the reduced risk of overdose make it an appealing alternative. Recent data on successful conversion for patients with chronic pain show a decrease in pain scores and increase in quality of life measurements after the beginning buprenorphine therapy for more than two months.

The first dose will be determined for each patient by a physician to ensure that the dosage of buprenorphine will be appropriate given the patient's current opioid dosage. There is the risk of withdrawal induced vaso-occlusive crisis (VOC).

Within 30 days prior to conversion to buprenorphine, a patient will take the ASCQ-Me, BPI, and two PROMIS surveys. Twenty-four hours prior to conversion, the patient will stop all opioid intake. The day of conversion, the patient will take a Clinical Opiate Withdrawal Scale (COWS) survey to determine whether they are in withdrawal. If so, the patient will begin buprenorphine conversion. They will also retake the aforementioned quality of life surveys. The patient will return on days 1, 14, 30, 90, and 180 to be evaluated.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Sickle Cell Disease, any genotype
• On disease modifying therapy (either chronic transfusions or hydroxyurea)
• On chronic daily full agonist opioid therapy with doses ranging from 90 to 400 morphine equivalents
• Have greater than 5 acute care visits in the last 6 months or have daily pain of 7 or higher on the Visual Analog Scale despite chronic opioid therapy.
• Able to provide consent
• Has medical insurance

Exclusion Criteria:

• Acute vaso-occlusive crisis on day of or day prior to buprenorphine initiation
• Use of methadone as long acting opioid (due to prolonged half-life and limited data in other populations)
• Use of illicit drugs as documented by urine toxicology screen (except for THC)
• Pregnancy
• Acute or severe bronchial asthma
• Hypersensitivity to buprenorphine or any component of the product
• Medical disorder, condition, or history that in the investigator's judgement would impair the patient's ability to participate or complete this study or render the patient to be inappropriate for enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Buprenorphine Arm; This is the main and only arm of the study. All patients in this arm will undergo the steps outlined in the protocol to convert to buprenorphine treatment.	Drug: buprenorphine; Patients in this study will receive dosages to be determined by a physician that are specific to each patient.; Other Names: Suboxone; Zubsolv; Buprenorphine Sublingual (SL)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Who Require Hospitalization Within 72 Hours Post Conversion From Full Agonist Opioids to Buprenorphine-based Pain Treatment	Data will be collected on need for hospitalization within 72 hours of conversion due to withdrawal induced vaso-occlusive crisis (VOC). If 2 out of the first 5 patients require hospitalization within 72 hours of conversion the study will be stopped and we will assess what changes need to be made in the protocol to decrease the risk of hospitalization triggered by the conversion.	72 hours after buprenorphine initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Number of Acute Care Visits Per Subject in the 6 Months Prior to Buprenorphine (BUP) Induction and in the 6 Months Post to BUP Induction	Change in the number of acute care visits per subject in the 6 months prior to BUP induction and in the 6 months post to BUP induction will be observed by comparing the mean number of acute care visits per patient- either to Emergency Department (ED) or to Sickle Cell Infusion Center - in the six months prior to BUP induction and in the six months post to BUP induction.	6 months pre BUP induction, 6 months post BUP induction
Change in Severity of Opiate Withdrawal, Based on the Clinical Opiate Withdrawal Scale (COWS) Score	Change in severity of opiate withdrawal will be observed by comparing the mean COWS score at BUP induction and 1 day post induction. All patients will be in opiate withdrawal at the time of buprenorphine induction and at the end of the first day of induction. The level of withdrawal will be measured by the COWS score, an 11-item scale designed to be administered by a clinician. The score ranges from 0-4 (no withdrawal), 5-12 (mild withdrawal), 13-24 (moderate withdrawal), 25-36 (severe withdrawal), and 36-48 (most severe withdrawal).	COWS score at BUP induction, COWS score at the end of the first day of induction
Number of Participants Continuing Buprenorphine Therapy After 6 Months of Induction	After induction, clinical team will continue to follow up with patients to see if they would like to continue buprenorphine therapy during the next 6 months after induction. The date of discontinuation and the reason why will be recorded. The number of participants reported in the outcome is the number of participants that continued buprenorphine therapy 6 months after induction.	6 months after induction

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Investigators: Principal Investigator: Sophie Lanzkron, MD, MHS, Johns Hopkins University

Publications and helpful links

General Publications

• Daitch D, Daitch J, Novinson D, Frey M, Mitnick C, Pergolizzi J Jr. Conversion from high-dose full-opioid agonists to sublingual buprenorphine reduces pain scores and improves quality of life for chronic pain patients. Pain Med. 2014 Dec;15(12):2087-94. doi: 10.1111/pme.12520. Epub 2014 Sep 12.
• Carroll CP, Lanzkron S, Haywood C Jr, Kiley K, Pejsa M, Moscou-Jackson G, Haythornthwaite JA, Campbell CM. Chronic Opioid Therapy and Central Sensitization in Sickle Cell Disease. Am J Prev Med. 2016 Jul;51(1 Suppl 1):S69-77. doi: 10.1016/j.amepre.2016.02.012.
• Platt OS, Thorington BD, Brambilla DJ, Milner PF, Rosse WF, Vichinsky E, Kinney TR. Pain in sickle cell disease. Rates and risk factors. N Engl J Med. 1991 Jul 4;325(1):11-6. doi: 10.1056/NEJM199107043250103.
• Wesson DR, Ling W. The Clinical Opiate Withdrawal Scale (COWS). J Psychoactive Drugs. 2003 Apr-Jun;35(2):253-9. doi: 10.1080/02791072.2003.10400007.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2018
• Primary Completion (ACTUAL): September 23, 2019
• Study Completion (ACTUAL): February 28, 2022

Study Registration Dates

• First Submitted: March 27, 2018
• First Submitted That Met QC Criteria: April 2, 2018
• First Posted (ACTUAL): April 10, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 25, 2022
• Last Update Submitted That Met QC Criteria: March 29, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Buprenorphine
• Other Study ID Numbers: IRB00159636

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data will be published at some point in the future but individual data will not be disclosed

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No