Buprenorphine for the Management of Pain in Children With Sickle Cell Disease

NCT07799571 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: P00051267183010
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn whether a single dose of buccal buprenorphine (BELBUCA) is safe when used in place and/or with full agonist opioids that would otherwise be started during a sickle cell pain crisis admission, in adolescents and young adults (ages 12-22) with sickle cell disease (SCD) who are hospitalized for acute pain. The main questions it aims to answer are:

• Is a single dose of buccal buprenorphine, given at doses between 75 and 450 micrograms, safe in this population?
• Does buccal buprenorphine reduce the amount of full agonist opioid pain medicine participants need through their patient-controlled analgesia (PCA) pump, and does it change pain scores?
• Are participants and their care team satisfied with pain management when buccal buprenorphine is used?
• What are the pharmacokinetic properties (how the body absorbs, distributes, and clears the drug) of buccal buprenorphine in this age group? This is a single-arm, open-label, dose-escalation study: every participant receives buccal buprenorphine, and there is no placebo or separate comparison group. Instead, researchers will compare each participant's own opioid use and pain scores in the 8 hours before receiving buccal buprenorphine to the 8 hours afterward, to see whether the dose reduces the need for additional opioid pain medicine. Participants will:
• Be treated first with standard-of-care patient-controlled analgesia (PCA) pain medicine (hydromorphone) during the early, acute-stabilization phase of their hospital stay.
• Once their pain is stable and they meet criteria to transition to oral opioids, as would happen under usual care, they will receive a single dose of buccal buprenorphine instead, at a dose (75, 150, 300, or 450 micrograms) assigned according to a dose-escalation design.
• Continue to have access to demand-only PCA pain medicine for breakthrough pain after the study dose.
• Undergo continuous monitoring of heart rate, oxygen level, and carbon dioxide level, plus pain and sedation checks every 4 hours, for 48 hours after the dose.
• Have blood samples collected, only when blood is already being drawn for clinical care, to help study how the body processes the drug.
• Complete a brief satisfaction survey about their pain management after the dose.
• Be contacted by phone or telehealth, and have their medical record reviewed, 30 days after the dose to check for any safety concerns.

Conditions

Sickle Cell Disease (SCD); Sickle Cell Disease Vaso-occlusive Crisis; Sickle Cell Anemia Crisis; Sickle Cell Anemia in Children; Sickle Cell Anemia (HbSS, or HbSβ-thalassemia0); Sickle Cell Hemoglobin C Disease; Pain Crisis

Keywords

Sickle Cell Disease; Sickle Cell Anemia; Vaso-Occlusive Crisis; Vaso-Occlusive Episode; Acute Pain; Pain Crisis; Buprenorphine; Buccal Buprenorphine; BELBUCA; Partial Opioid Agonist; Opioid-Sparing; Hydromorphone; Bayesian Optimal Interval Design; Phase 1 Trial; Adolescent; Pediatric; Young Adult; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Incidence of Protocol-Defined Safety Events

  Safety is defined operationally as the absence of: (1) requirement for transfer to a higher level of care (such as the ICU), acute chest syndrome, stroke, or any acute life-threatening event requiring emergent medical intervention; (2) severe somnolence (Modified Ramsay Sedation Score ≥7) and/or disorientation persisting despite routine efforts to awaken; (3) severe hypoxemia (SpO2 decrease of ≥3-4% from pre-dose SpO2, or \<88%, whichever is lower, despite treatment); (4) severe hypoventilation (respiratory rate \<6 breaths/min or ETCO2/TcCO2 \>65 mmHg for \>5 minutes despite routine efforts to awaken); (5) administration of naloxone for sedation or respiratory depression; (6) any CTCAE v5.0 Grade ≥3 adverse event attributed to the study drug.

  Within the 48-hour observation window following study drug (buccal buprenorphine) administration

Secondary Outcomes (3)

• Change in Numeric Rating Scale (NRS) Pain Scores

  8-hour period before the buprenorphine dose, compared to the 8-hour period after the dose, and an 8-hour epoch beginning 12 hours after the dose

• Decrement in Cumulative Full-Agonist Opioid (PCA) Consumption

  8-hour period before the buprenorphine dose, compared to the 8-hour period after the dose, and an 8-hour epoch beginning 12 hours after the dose

• Patient/Parent Satisfaction with Pain Management

  48 hours after study drug administration, through hospital discharge

Other Outcomes (3)

• Plasma Buprenorphine Concentration

  From time of study drug administration through 48 hours post-dose

• Provider Satisfaction with Pain Management

  48 hours after study drug administration, through hospital discharge

• Plasma Norbuprenorphine Concentration

  From time of study drug administration through 48 hours post-dose

Study Arms (1)

Buccal Buprenorphine (Dose-Escalation)

EXPERIMENTAL

Participants receive standard-of-care demand-and-continuous hydromorphone PCA during acute stabilization (Phase 1). Once transition-readiness criteria are met (Phase 2), the continuous PCA infusion is discontinued and, after a minimum one-hour equilibration period, participants receive a single buccal dose of buprenorphine (75, 150, 300, or 450 mcg, depending on dose-escalation cohort assignment per the BOIN design) in place of the oral opioid that would otherwise be started, while continuing demand-only PCA for breakthrough pain.

Drug: Buprenorphine Buccal Film [Belbuca]

Interventions

Buprenorphine Buccal Film [Belbuca] DRUG

A single buccal dose of buprenorphine (BELBUCA), administered once between 8:00 AM and 3:00 PM on the qualifying study day. Dose is assigned by dose-escalation cohort (75 mcg, 150 mcg, 300 mcg, or 450 mcg) per a Bayesian Optimal Interval (BOIN) design targeting a dose-limiting toxicity rate of 0.25.

Also known as: buprenorphine, Belbuca

Buccal Buprenorphine (Dose-Escalation)

Eligibility Criteria

• Age: 12 Years - 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• SCD diagnosis (confirmed by Hemoglobin electrophoresis prior to consent)
• years of age who present for acute sickle cell pain crisis
• Weight \> 50kg
• Negative pregnancy test during index admission for patients of childbearing potential

You may not qualify if:

• Patient refusal to participate
• Hypersensitivity (e.g. anaphylaxis) to buprenorphine
• Lack of informed consent or assent
• \< 12 years of age
• Weight \< 50kg
• Significant respiratory depression
• Presence of gastrointestinal obstruction, including paralytic ileus
• History of seizures
• Presence of shock physiology
• Severe hepatic impairment (Child-Pugh score of C or worse)
• Concurrent strong CYP3A4 inhibitors/inducers
• Current Monoamine Oxidase Inhibitor (MAOI) use or use within 14 days
• Active breastfeeding

Sponsors & Collaborators

• Natasha Archer: lead

Study Sites (1)

Boston Children's Hospital

Boston, Massachusetts, 02215, United States

Location

Related Publications (6)

• Carroll, Christopher Patrick, Elizabeth J. Prince, Ashley Lauriello, Lydia H. Pecker, and Sophie M. Lanzkron. "Acute Pain Treatment in Patients with Sickle Cell Disease Transitioned to Buprenorphine: Evidence of Equivalent Pain Relief." Journal of Sickle Cell Disease 2, no. 1 (2025): yoaf014. https://doi.org/10.1093/jscdis/yoaf014.

  BACKGROUND

• Attina G, Romano A, Triarico S, Mastrangelo S, Maurizi P, Ruggiero A. Transdermal buprenorphine for pain management in children. Drugs Context. 2021 Sep 14;10:2021-6-1. doi: 10.7573/dic.2021-6-1. eCollection 2021.

  PMID: 34567202 BACKGROUND

• deBettencourt J, Nagy M, Rotman C, Greco C, Berde C, Archer NM. Buprenorphine for Children and Adolescents with Sickle Cell Disease: A Scoping Review. Children (Basel). 2026 Mar 10;13(3):388. doi: 10.3390/children13030388.

  PMID: 41897100 BACKGROUND

• Webster LR, Cater J, Smith T. Pharmacokinetics of Buprenorphine Buccal Film and Orally-administered Oxycodone in a Respiratory Study: An Analysis of Secondary Outcomes from a Randomized Controlled Trial. Pain Ther. 2022 Sep;11(3):817-825. doi: 10.1007/s40122-022-00380-2. Epub 2022 May 7.

  PMID: 35524938 BACKGROUND

• Walsh SL, Preston KL, Stitzer ML, Cone EJ, Bigelow GE. Clinical pharmacology of buprenorphine: ceiling effects at high doses. Clin Pharmacol Ther. 1994 May;55(5):569-80. doi: 10.1038/clpt.1994.71.

  PMID: 8181201 BACKGROUND

• Spinella S, McCarthy R. Buprenorphine for Pain: A Narrative Review and Practical Applications. Am J Med. 2024 May;137(5):406-413. doi: 10.1016/j.amjmed.2024.01.022. Epub 2024 Feb 9.

  PMID: 38340973 BACKGROUND

MeSH Terms

Conditions

Anemia, Sickle Cell; Vaso-Occlusive Crises; Hemoglobin SC Disease; Acute Pain

Interventions

Buprenorphine

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Natasha Archer, MD

  Dana-Farber/Boston Children's Cancer and Blood Disorders Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Natasha Archer, MD

CONTACT

617-632-5508; natasha.archer@childrens.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Sickle Cell Program, Dana Farber/Boston Children's Cancer and Blood Disorders Center

Model Details: Phase 1, single-dose, open-label, single-institution, dose-escalation safety study

Study Record Dates

• First Submitted: August 19, 2026
• First Posted: September 2, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): October 1, 2031
• Study Completion (Estimated): October 1, 2032
• Last Updated: September 2, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)