Verapamil Effect in Cystic Fibrosis-related Dysglycemia

NCT07688070 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2390110
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

The investigators are conducting a pilot open-label pre/post interventional trial in adolescents and adults with cystic fibrosis (CF) and abnormal glucose tolerance or early CF-related diabetes mellitus (CFRD) to assess the safety and efficacy of verapamil on beta cell function and dysglycemia.

Conditions

Cystic Fibrosis Related Diabetes; Cystic Fibrosis (CF); Abnormal Glucose Tolerance

Keywords

cystic fibrosis related diabetes; mixed meal tolerance test; verapamil; beta cell function; continuous glucose monitoring; abnormal glucose tolerance; cystic fibrosis

Outcome Measures

Primary Outcomes (1)

• Change in 30-minute C-peptide area under the curve after mixed-meal tolerance test

  laboratory test, measured in ng/mL

  Baseline, 6 months

Secondary Outcomes (30)

• Change in 180 minute C-peptide area under the curve after mixed-meal tolerance test

  Baseline, 6 months

• Change in insulin level area under the curve after mixed-meal tolerance test

  Baseline, 6 months

• Change in proinsulin area under the curve after mixed-meal tolerance test

  Baseline, 6 months

• Change in glucose area under the curve after mixed-meal tolerance test

  Baseline, 6 months

• Change in hemoglobin A1c

  Baseline, 6 months

Study Arms (1)

Intervention Arm

EXPERIMENTAL

verapamil hydrochloride

Drug: Verapamil Hydrochloride

Interventions

Verapamil Hydrochloride DRUG

Verapamil extended release (ER) will be initiated at a dose of 120mg daily and up-titrated over six weeks to target dose of 360mg daily as tolerated.

Intervention Arm

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 14 years and older
• Genetically-confirmed diagnosis of cystic fibrosis
• Clinical diagnosis of pancreatic insufficiency, defined as requiring pancreatic enzyme replacement therapy (PERT)
• Diagnosis of AGT or CFRD within 3-months of study enrollment
• AGT is defined as having either a OGTT 2-hour glucose \>140 mg/dL and \<200 mg/dL or OGTT 1-hour glucose \>200 mg/dL
• CFRD is defined as having a fasting glucose \>126 mg/dL and/or OGTT 2-hour glucose \>200 mg/dL
• Willing to attempt to maximize verapamil to the goal study dosage of 360 mg PO daily
• If taking elexacaftor/tezacaftor/ivacaftor (ETI), willing to adjust dosing

You may not qualify if:

• Severe lung disease indicated by forced expiratory volume in 1 second (FEV1) \<50% predicted on most recent spirometry testing
• Body mass index (BMI) \<18 kg/m2
• Weight \<50 kg
• Current or planned pregnancy within the next 6 months
• Treatment with IV antibiotics for a CF exacerbation within 1 month
• Systemic supraphysiologic glucocorticoid use within 1 month
• Initiation or discontinuation of a CFTR modulator within 3 months (i.e. recent change in CFTR modulator formulation/usage)
• Current use of insulin, a GLP-1 receptor agonist, or oral anti-diabetic agent
• Most recent HbA1c \>7%
• Not taking a CFTR modulator due to genotype-ineligibility
• Current use of vanzacaftor/tezacaftor/deutivcaftor
• Known hypersensitivity to verapamil
• Blood pressure (BP) \<90/60 (adults) or \<5th centile for age and gender (youth) in 2 out of 3 measurements
• Heart rate (HR) \<60 bpm (adults) or \<2nd centile for age and gender (youth) in 2 out of 3 measurements
• History of previously diagnosed vasovagal syncopal episodes related to hypotension

Sponsors & Collaborators

• Rhode Island Hospital: lead

Study Sites (2)

Diabetes Research Center, Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Related Publications (5)

• Forlenza GP, McVean J, Beck RW, Bauza C, Bailey R, Buckingham B, DiMeglio LA, Sherr JL, Clements M, Neyman A, Evans-Molina C, Sims EK, Messer LH, Ekhlaspour L, McDonough R, Van Name M, Rojas D, Beasley S, DuBose S, Kollman C, Moran A; CLVer Study Group. Effect of Verapamil on Pancreatic Beta Cell Function in Newly Diagnosed Pediatric Type 1 Diabetes: A Randomized Clinical Trial. JAMA. 2023 Mar 28;329(12):990-999. doi: 10.1001/jama.2023.2064.

  PMID: 36826844 BACKGROUND

• Ntimbane T, Krishnamoorthy P, Huot C, Legault L, Jacob SV, Brunet S, Levy E, Gueraud F, Lands LC, Comte B. Oxidative stress and cystic fibrosis-related diabetes: a pilot study in children. J Cyst Fibros. 2008 Sep;7(5):373-84. doi: 10.1016/j.jcf.2008.01.004. Epub 2008 Apr 16.

  PMID: 18420468 BACKGROUND

• Umashankar B, Eliasson L, Ooi CY, Kim KW, Shaw JAM, Waters SA. Beyond insulin: Unraveling the complex interplay of ER stress, oxidative damage, and CFTR modulation in CFRD. J Cyst Fibros. 2024 Sep;23(5):842-852. doi: 10.1016/j.jcf.2024.06.004. Epub 2024 Jun 18.

  PMID: 38897882 BACKGROUND

• Ode KL, Ballman M, Battezzati A, Brennan A, Chan CL, Hameed S, Ismail HM, Kelly A, Moran AM, Rabasa-Lhoret R, Saxby NA, Craig ME. ISPAD Clinical Practice Consensus Guidelines 2022: Management of cystic fibrosis-related diabetes in children and adolescents. Pediatr Diabetes. 2022 Dec;23(8):1212-1228. doi: 10.1111/pedi.13453. No abstract available.

  PMID: 36537525 BACKGROUND

• Norris AW, Ode KL, Merjaneh L, Sanda S, Yi Y, Sun X, Engelhardt JF, Hull RL. Survival in a bad neighborhood: pancreatic islets in cystic fibrosis. J Endocrinol. 2019 Apr;241(1):R35-R50. doi: 10.1530/JOE-18-0468.

  PMID: 30759072 BACKGROUND

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Verapamil

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Phenethylamines; Ethylamines; Amines; Organic Chemicals

Central Study Contacts

Kevin J Scully

CONTACT

401-444-5504; kevin_scully@brown.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator; Pediatric Endocrinologist

Model Details: Pre/post interventional trial

Study Record Dates

• First Submitted: June 30, 2026
• First Posted: July 7, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): August 31, 2028
• Last Updated: July 9, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)