The Impact of Insulin Therapy on Protein Turnover in Pre-Diabetic Cystic Fibrosis Patients

NCT02496780 | Terminated Phase 2 Results

• 1 other identifier: PEDS-2015-23490
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 2

Brief Summary

Insulin replacement therapy may be effective in breaking the cycle of protein catabolism, undernutrition and overall clinical deterioration in pre-diabetic, insulin insufficient CF youth because of its potent anabolic effect. A significant number of CF patients might benefit from this therapeutic approach with a substantial impact on morbidity and mortality.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Endogenous Protein Breakdown (Flux) After 4 Weeks of Insulin/Placebo Therapy, CF Patients

  Primary endpoint. Determined from a stable isotope-labelled test meal. In the primary analysis, patients on both forms of insulin were first combined and compared to CF patients on placebo. In a second analysis, the two insulin types were separately compared to eachother and to placebo. Change in rate of endogenous protein breakdown (Ra-end) change from baseline (pre-treatment) and after 4 wks of study drug

  4 weeks

Secondary Outcomes (1)

• Baseline Protein Turnover (Flux), CF Patients vs Healthy Controls

  baseline

Study Arms (4)

placebo

PLACEBO COMPARATOR

once or 3x daily injectable placebo (insulin diluent)

Drug: placebo

basal insulin levemir

EXPERIMENTAL

once daily basal insulin therapy with insulin levemir

Drug: levemir insulin

rapid-acting insulin Novolog

EXPERIMENTAL

pre-meal rapid-acting insulin 3x/day with insulin novolog

Drug: novolog insulin

Healthy controls

NO INTERVENTION

Healthy controls matched by age, gender and BMI to CF participants. These participants are only used for baseline information, no intervention or outcome measure collected

Interventions

novolog insulin DRUG

3x daily rapid-acting insulin

Also known as: apart

rapid-acting insulin Novolog

levemir insulin DRUG

basal insulin once a day

Also known as: detemir

basal insulin levemir

placebo DRUG

once or 3x daily

Also known as: insulin diluent

placebo

Eligibility Criteria

• Age: 10 Years - 25 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis of cystic fibrosis, age 10-25 years
• A standard routine annual OGTT performed within 12 months of randomization
• Abnormal glucose tolerance, with a fasting glucose level \<126 mg/dl and
• The 1-hr OGTT glucose is ≥200 mg/dl but the 2-hr glucose is \<140 (INDET), OR
• The 2-hour OGTT glucose is 140-199 mg/dl (impaired glucose tolerance, IGT).

You may not qualify if:

• Diagnosis of CFRD, Consensus Conference definition (45)
• Previous organ transplant, or transplant imminent during study period
• BMI percentile \>95
• Treatment with systemic glucocorticoids (nasal or inhaled glucocorticoids are acceptable)
• Therapy with growth hormone or Megace
• Nighttime continuous drip gastrostomy/jejunostomy feedings
• Pregnancy or breast-feeding or plans to become pregnant during study period
• Any change in medications during the 3 months prior to the study
• Exception: the new corrector/potentiator combination drug lumacaftor/ivacaftor is expected to get FDA approval in early 2015, and most CF patients with severe genotypes, including many eligible for this proposal, will receive this drug. This is not a contraindication to participation in the current proposal (and participation in other studies is not contraindicated in the PROSPECT post-marketing drug study). Though the primary effects of the combination therapy appear to be apparent after 1 month, we will wait 6 months after initiation of lumacaftor/ivacaftor before enrollment in this study to make sure subjects are in a steady state.
• Any anticipated change in medication during the 3 month study period
• Acute illness in the 6 weeks prior to enrollment

Sponsors & Collaborators

• University of Minnesota: lead

Study Sites (2)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Children's Hospitals and Clinics of Minnesota

Saint Paul, Minnesota, United States

Location

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Insulin Aspart; Insulin Detemir

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)

Insulin, Short-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Insulin, Long-Acting

Limitations and Caveats

The study was terminated before reaching the planned sample size, after a futility analysis suggested a full sample size would not lead to a positive result.

Results Point of Contact

• Title: Antoinette Moran
• Organization: University of Minnesota

moran001@umn.edu

612-624-5409

Study Officials

• Antoinette Moran, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2015
• First Posted: July 14, 2015
• Study Start: August 1, 2015
• Primary Completion: July 1, 2022
• Study Completion: July 1, 2022
• Last Updated: March 17, 2025
• Results First Posted: March 17, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)