Sickle Cell DiseasePhase 2NCT03492099

Assessing the Safety of Buprenorphine in People With Sickle Cell Disease

A Phase 2 study testing buprenorphine in people with Sickle Cell Disease, run by Johns Hopkins University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Sickle Cell Disease
What is being tested?: buprenorphine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 47 participants
Where: 1 siteUnited States
Study dates: 1 Aug 2018to 28 Feb 2022
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Johns Hopkins Hospital
Baltimore, Maryland, 21205

Other trials in United States

About this study

Read the 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.

Conditions: Sickle Cell Disease
Being tested: buprenorphine
Medical subject headings: Anemia, Sickle Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

buprenorphineDrug
Also called Zubsolv, Suboxone, Buprenorphine Sublingual (SL)
Patients in this study will receive dosages to be determined by a physician that are specific to each patient.

Study groups in NCT03492099
Study group	Role	What they receive
Buprenorphine Arm	Experimental	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. Receives: Drug: buprenorphine

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 72 hours after buprenorphine initiation

Secondary outcomes (3)

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.
Measured: 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).
Measured: 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.
Measured: 6 months after induction

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Aug 201828 Feb 2022

First posted10 Apr 2018
Study start1 Aug 2018
Primary completion23 Sep 2019
Study completion28 Feb 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 47 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03492099
Sponsor's protocol ID: IRB00159636
Status last verified: Mar 2022
First submitted: 27 Mar 2018
Last updated: 25 Apr 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No: Data will be published at some point in the future but individual data will not be disclosed

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.
PubMed 25220043
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.
PubMed 27320469
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.
PubMed 1710777
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.
PubMed 12924748

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 1/2
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Long-term Mitapivat Dosing in Subjects With Stable Sickle Cell Disease: An Extension of a Phase I Pilot Study of Mitapivat
Sickle Cell Disease, Hemolytic Anemia
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
RecruitingPhase 1
Study to Evaluate the Safety and Tolerability of Escalating Doses of Fostamatinib in Subjects With Stable Sickle Cell Disease
Sickle Cell Disorders, Sickle Cell Disease
RecruitingPhase 4
Clinical and Biomarker Effects of Depot Medroxyprogesterone Acetate in Females With Sickle Cell Disease
Sickle Cell Disease (SCD), Vaso-Occlusive Pain Episode in Sickle Cell Disease
Not yet recruitingPhase 1
Buprenorphine for the Management of Pain in Children With Sickle Cell Disease
Sickle Cell Disease (SCD), Sickle Cell Disease Vaso-occlusive Crisis

All Sickle Cell Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 25 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Assessing the Safety of Buprenorphine in People With Sickle Cell Disease
ClinicalTrials.gov ID: NCT03492099
Acronym / sponsor ID: IRB00159636
Conditions: Sickle Cell Disease
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 47 participants (actual)
Lead sponsor: Johns Hopkins UniversityUniversity, hospital or other
Study start: 1 Aug 2018 (actual)
Primary completion: 23 Sep 2019 (actual)
Study completion: 28 Feb 2022 (actual)
First posted: 10 Apr 2018 (actual)
Results: Posted 1 Oct 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Buprenorphine Arm	Experimental	Drug: buprenorphineThis 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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

Key exclusion criteria (7 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
buprenorphineAlso: Zubsolv, Suboxone, Buprenorphine Sublingual (SL)Patients in this study will receive dosages to be determined by a physician that are specific to each patient.	Drug	Buprenorphine Arm

Primary outcome

Number of Subjects Who Require Hospitalization Within 72 Hours Post Conversion From Full Agonist Opioids to Buprenorphine-based Pain Treatment
Time frame: 72 hours after buprenorphine initiation
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.

3 secondary outcomes

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
Time frame: 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
Time frame: 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
Time frame: 6 months after induction

Results and safety

Results posted to the registry on 1 Oct 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Buprenorphine Arm	47	43

Primary outcome: Number of Subjects Who Require Hospitalization Within 72 Hours Post Conversion From Full Agonist Opioids to Buprenorphine-based Pain Treatment

Time frame: 72 hours after buprenorphine initiation. Count of participants. Unit: Participants

Measure	Buprenorphine Arm n = 43
Value	1

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Within 72 hours of induction. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Buprenorphine Arm	1 of 47 (2.1%)	9 of 47 (19.1%)	0 of 47

Limitations and caveats (from the sponsor): The study was not randomized nor controlled. The participant pool was limited to those patients who consented to have their data reported; and among those prospectively enrolled, to those who accepted induction. In addition, not all inductions followed the same procedure. In particular, those that were performed inpatient might have a number of biases in patient selection and capacity to detect adverse events.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 25220043Daitch 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.
Background: PubMed 27320469Carroll 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.
Background: PubMed 1710777Platt 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.
Background: PubMed 12924748Wesson 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.
Individual participant dataSharing planned: No. Data will be published at some point in the future but individual data will not be disclosed

Related trials for Sickle Cell Disease

Active, not recruitingPhase 1/2
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Long-term Mitapivat Dosing in Subjects With Stable Sickle Cell Disease: An Extension of a Phase I Pilot Study of Mitapivat
Sickle Cell Disease, Hemolytic Anemia
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
RecruitingPhase 1
Study to Evaluate the Safety and Tolerability of Escalating Doses of Fostamatinib in Subjects With Stable Sickle Cell Disease
Sickle Cell Disorders, Sickle Cell Disease
RecruitingPhase 4
Clinical and Biomarker Effects of Depot Medroxyprogesterone Acetate in Females With Sickle Cell Disease
Sickle Cell Disease (SCD), Vaso-Occlusive Pain Episode in Sickle Cell Disease
Not yet recruitingPhase 1
Buprenorphine for the Management of Pain in Children With Sickle Cell Disease
Sickle Cell Disease (SCD), Sickle Cell Disease Vaso-occlusive Crisis

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Sophie Lanzkron, MD, MHS principal investigator

Johns Hopkins University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing buprenorphine in people with Sickle Cell Disease, run by Johns Hopkins University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Subjects Who Require Hospitalization Within 72 Hours Post Conversion From Full Agonist Opioids to Buprenorphine-based Pain Treatment (time frame: 72 hours after buprenorphine initiation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03492099, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2022.