Cystic FibrosisPhase 2/3NCT02496780
The Impact of Insulin Therapy on Protein Turnover in Pre-Diabetic Cystic Fibrosis Patients
A Phase 2/3 study testing novolog insulin and levemir insulin in people with Cystic Fibrosis, run by University of Minnesota at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 10 to 25 yearsHealthy volunteers can take part
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- novolog insulin and levemir insulin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 65 participants
- Where
- 2 sitesUnited States
- Study dates
- Aug 2015to Jul 2022
- Phase
- Phase 2/3
- 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 10 to 25 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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).
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Minnesota
Minneapolis, Minnesota, 55455
Children's Hospitals and Clinics of Minnesota
Saint Paul, Minnesota
About this study
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.
Read the detailed description
Insulin insufficiency related to pancreatic fibrosis and β-cell dysfunction is present in almost every cystic fibrosis (CF) patient. Progressive abnormalities in insulin secretion begin in childhood, and, in adults, CF related diabetes (CFRD) is eventually present in more than half of the CF population. CFRD is associated with weight loss, protein catabolism, loss of lean body mass (LBM), and early death from lung disease and malnutrition. The negative consequences of diabetes are just the "tip of the iceberg", since clinical deterioration has been documented to begin in the pre-diabetic period. Non-diabetic glucose tolerance abnormalities in CF are associated with protein catabolism, weight loss and lung function decline, all of which correlate with the severity of insulin secretory defects, suggesting a key pathologic role for insulin insufficiency. Insulin is a potent anabolic hormone, critical for maintenance of body weight and muscle mass. In a placebo-controlled clinical trial, insulin therapy improved body mass index (BMI) and LBM in patients with very early CFRD (CFRD without fasting hyperglycemia), and this is now standard care for these patients. There is growing preliminary evidence that insulin therapy is beneficial even earlier, in CF patients with pre-diabetes due to insulin insufficiency. Given the universal prevalence of insulin insufficiency in CF, the high lifetime risk of developing diabetes, the clinical impact of insulin insufficiency on protein catabolism and survival in CF, and the critical importance of maintaining body weight and LBM in this population, there is an urgent need to determine whether insulin replacement therapy should be instituted for anabolic purposes prior to the actual onset of diabetes and, if so, to ascertain the optimal regimen. The current protocol describes a double-blind, placebo-controlled trial to determine whether insulin therapy improves protein catabolism in youth with CF and abnormal glucose tolerance, and to explore differences in efficacy between multiple daily pre-meal insulin dosing (as is currently standard for early CFRD) versus a more convenient once daily basal insulin dose (as has been used in small uncontrolled pilot studies). The findings of this study will provide a mechanistic rationale for instituting insulin in youth with CF and pre-diabetes, and will inform both research studies and clinical practice as to the best regimen for insulin delivery in this population.
- Conditions
- Cystic Fibrosis
- Being tested
- novolog insulin, levemir insulin, placebo
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
novolog insulinDrug
Also called apart
3x daily rapid-acting insulin
levemir insulinDrug
Also called detemir
basal insulin once a day
placeboDrug
Also called insulin diluent
once or 3x daily
| Study group | Role | What they receive |
|---|---|---|
| placebo | Placebo comparator | once or 3x daily injectable placebo (insulin diluent) Receives: Drug: placebo |
| basal insulin levemir | Experimental | once daily basal insulin therapy with insulin levemir Receives: Drug: levemir insulin |
| rapid-acting insulin Novolog | Experimental | pre-meal rapid-acting insulin 3x/day with insulin novolog Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 4 weeks
Secondary outcomes (1)
Baseline Protein Turnover (Flux), CF Patients vs Healthy Controls
Endogenous protein breakdown at baseline (Ra-end). CF patients vs healthy controls.
Rate of endogenous protein breakdown (Ra-end), nadir (µmol/kg(LBM)/min)
Measured: baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2015 (estimated)
- Study startAug 2015
- Primary completionJul 2022
- Study completionJul 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.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by University of MinnesotaThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Antoinette Moran, MD, Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02496780
- Sponsor's protocol ID
- PEDS-2015-23490
- Status last verified
- Mar 2025
- First submitted
- 18 Jun 2015
- Last updated
- 17 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No: No, individual data will remain with the PI.
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Impact of Insulin Therapy on Protein Turnover in Pre-Diabetic Cystic Fibrosis Patients
- ClinicalTrials.gov ID
- NCT02496780
- Acronym / sponsor ID
- PEDS-2015-23490
- Conditions
- Cystic Fibrosis
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 65 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Study start
- Aug 2015 (actual)
- Primary completion
- Jul 2022 (actual)
- Study completion
- Jul 2022 (actual)
- First posted
- 14 Jul 2015 (estimated)
- Results
- Posted 17 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Insulin insufficiency related to pancreatic fibrosis and β-cell dysfunction is present in almost every cystic fibrosis (CF) patient. Progressive abnormalities in insulin secretion begin in childhood, and, in adults, CF related diabetes (CFRD) is eventually present in more than half of the CF population. CFRD is associated with weight loss, protein catabolism, loss of lean body mass (LBM), and early death from lung disease and malnutrition. The negative consequences of diabetes are just the "tip of the iceberg", since clinical deterioration has been documented to begin in the pre-diabetic period. Non-diabetic glucose tolerance abnormalities in CF are associated with protein catabolism, weight loss and lung function decline, all of which correlate with the severity of insulin secretory defects, suggesting a key pathologic role for insulin insufficiency. Insulin is a potent anabolic hormone, critical for maintenance of body weight and muscle mass. In a placebo-controlled clinical trial, insulin therapy improved body mass index (BMI) and LBM in patients with very early CFRD (CFRD without fasting hyperglycemia), and this is now standard care for these patients. There is growing preliminary evidence that insulin therapy is beneficial even earlier, in CF patients with pre-diabetes due to insulin insufficiency. Given the universal prevalence of insulin insufficiency in CF, the high lifetime risk of developing diabetes, the clinical impact of insulin insufficiency on protein catabolism and survival in CF, and the critical importance of maintaining body weight and LBM in this population, there is an urgent need to determine whether insulin replacement therapy should be instituted for anabolic purposes prior to the actual onset of diabetes and, if so, to ascertain the optimal regimen. The current protocol describes a double-blind, placebo-controlled trial to determine whether insulin therapy improves protein catabolism in youth with CF and abnormal glucose tolerance, and to explore differences in efficacy between multiple daily pre-meal insulin dosing (as is currently standard for early CFRD) versus a more convenient once daily basal insulin dose (as has been used in small uncontrolled pilot studies). The findings of this study will provide a mechanistic rationale for instituting insulin in youth with CF and pre-diabetes, and will inform both research studies and clinical practice as to the best regimen for insulin delivery in this population.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| placebo | Placebo comparator | Drug: placeboonce or 3x daily injectable placebo (insulin diluent) |
| basal insulin levemir | Experimental | Drug: levemir insulinonce daily basal insulin therapy with insulin levemir |
| rapid-acting insulin Novolog | Experimental | Drug: novolog insulinpre-meal rapid-acting insulin 3x/day with insulin novolog |
| 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 |
Who may qualify
- Ages
- 10 to 25 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (11 listed)
- 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
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 |
|---|---|---|
| novolog insulinAlso: apart3x daily rapid-acting insulin | Drug | rapid-acting insulin Novolog |
| levemir insulinAlso: detemirbasal insulin once a day | Drug | basal insulin levemir |
| placeboAlso: insulin diluentonce or 3x daily | Drug | placebo |
Primary outcome
Change From Baseline in Endogenous Protein Breakdown (Flux) After 4 Weeks of Insulin/Placebo Therapy, CF Patients
Time frame: 4 weeks
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
1 secondary outcome
Baseline Protein Turnover (Flux), CF Patients vs Healthy Controls
Time frame: baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. No, individual data will remain with the PI.
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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.
Antoinette Moran, MD principal investigator
University of Minnesota
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing novolog insulin and levemir insulin in people with Cystic Fibrosis, run by University of Minnesota at 2 sites 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 5 inclusion and 11 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: stopped early, as of the sponsor's last update on 17 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 17 Mar 2025). 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?
Change From Baseline in Endogenous Protein Breakdown (Flux) After 4 Weeks of Insulin/Placebo Therapy, CF Patients (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Mar 2025.