Trial Outcomes & Findings for The Impact of Insulin Therapy on Protein Turnover in Pre-Diabetic Cystic Fibrosis Patients (NCT NCT02496780)

Last Updated: 2025-03-17

Results Overview

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

Recruitment status

TERMINATED

Study phase

PHASE2/PHASE3

Target enrollment

65 participants

Primary outcome timeframe

4 weeks

Results posted on

2025-03-17

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo once or 3x daily injectable placebo (insulin diluent) placebo: once or 3x daily	Basal Insulin Levemir once daily basal insulin therapy with insulin levemir levemir insulin: basal insulin once a day	Rapid-acting Insulin Novolog pre-meal rapid-acting insulin 3x/day with insulin novolog novolog insulin: 3x daily rapid-acting insulin	Healthy Controls 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
Overall Study STARTED	12	13	15	25
Overall Study COMPLETED	11	9	10	20
Overall Study NOT COMPLETED	1	4	5	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=11 Participants once or 3x daily injectable placebo (insulin diluent) placebo: once or 3x daily	Basal Insulin Levemir n=11 Participants once daily basal insulin therapy with insulin levemir levemir insulin: basal insulin once a day	Rapid-acting Insulin Novolog n=15 Participants pre-meal rapid-acting insulin 3x/day with insulin novolog novolog insulin: 3x daily rapid-acting insulin	Healthy Controls n=20 Participants 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	Total n=57 Participants Total of all reporting groups
Age, Categorical <=18 years	4 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	10 Participants n=4 Participants	25 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants	10 Participants n=4 Participants	32 Participants n=21 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants	9 Participants n=4 Participants	26 Participants n=21 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants	11 Participants n=4 Participants	31 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants	10 Participants n=7 Participants	13 Participants n=5 Participants	18 Participants n=4 Participants	52 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: 4 weeks

Population: Healthy controls did not participant in the primary aim

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants once or 3x daily injectable placebo (insulin diluent) placebo: once or 3x daily	Basal Insulin Levemir n=9 Participants once daily basal insulin therapy with insulin levemir levemir insulin: basal insulin once a day	Rapid-acting Insulin Novolog n=10 Participants pre-meal rapid-acting insulin 3x/day with insulin novolog novolog insulin: 3x daily rapid-acting insulin
Change From Baseline in Endogenous Protein Breakdown (Flux) After 4 Weeks of Insulin/Placebo Therapy, CF Patients	-0.01 µmol/kg(LBM)/min Standard Error 0.047	0.022 µmol/kg(LBM)/min Standard Error 0.046	0.0004 µmol/kg(LBM)/min Standard Error 0.06

SECONDARY outcome

Timeframe: baseline

Population: Note that for this secondary endpoint we assessed the baseline data of the entire CF population versus controls. Thus, in this pre-treatment population, all CF patients were included as a group regardless of what arm they were later randomized to. This was the only comparison between CF and healthy controls, who were matched for age, gender and BMI to CF participants.

Endogenous protein breakdown at baseline (Ra-end). CF patients vs healthy controls. Rate of endogenous protein breakdown (Ra-end), nadir (µmol/kg(LBM)/min)

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants once or 3x daily injectable placebo (insulin diluent) placebo: once or 3x daily	Basal Insulin Levemir n=20 Participants once daily basal insulin therapy with insulin levemir levemir insulin: basal insulin once a day	Rapid-acting Insulin Novolog pre-meal rapid-acting insulin 3x/day with insulin novolog novolog insulin: 3x daily rapid-acting insulin
Baseline Protein Turnover (Flux), CF Patients vs Healthy Controls	0.963 µmol/kg(LBM)/min Standard Error 0.135	0.921 µmol/kg(LBM)/min Standard Error 0.219	—

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Basal Insulin Levemir

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Rapid-acting Insulin Novolog

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Healthy Controls

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Placebo n=12 participants at risk once or 3x daily injectable placebo (insulin diluent) placebo: once or 3x daily	Basal Insulin Levemir n=13 participants at risk once daily basal insulin therapy with insulin levemir levemir insulin: basal insulin once a day	Rapid-acting Insulin Novolog n=15 participants at risk pre-meal rapid-acting insulin 3x/day with insulin novolog novolog insulin: 3x daily rapid-acting insulin	Healthy Controls n=25 participants at risk 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
Gastrointestinal disorders unable to consume test meal	8.3% 1/12 • Number of events 1 • Adverse event data were collected over 8 weeks. The subjects had their baseline test meal at time 0, insulin / placebo was given weeks 2-8, and the second test meal (for calculation of primary endpoint) was at 6 weeks.	7.7% 1/13 • Number of events 1 • Adverse event data were collected over 8 weeks. The subjects had their baseline test meal at time 0, insulin / placebo was given weeks 2-8, and the second test meal (for calculation of primary endpoint) was at 6 weeks.	0.00% 0/15 • Adverse event data were collected over 8 weeks. The subjects had their baseline test meal at time 0, insulin / placebo was given weeks 2-8, and the second test meal (for calculation of primary endpoint) was at 6 weeks.	8.0% 2/25 • Number of events 2 • Adverse event data were collected over 8 weeks. The subjects had their baseline test meal at time 0, insulin / placebo was given weeks 2-8, and the second test meal (for calculation of primary endpoint) was at 6 weeks.
Gastrointestinal disorders vomiting with test meal	0.00% 0/12 • Adverse event data were collected over 8 weeks. The subjects had their baseline test meal at time 0, insulin / placebo was given weeks 2-8, and the second test meal (for calculation of primary endpoint) was at 6 weeks.	7.7% 1/13 • Number of events 1 • Adverse event data were collected over 8 weeks. The subjects had their baseline test meal at time 0, insulin / placebo was given weeks 2-8, and the second test meal (for calculation of primary endpoint) was at 6 weeks.	0.00% 0/15 • Adverse event data were collected over 8 weeks. The subjects had their baseline test meal at time 0, insulin / placebo was given weeks 2-8, and the second test meal (for calculation of primary endpoint) was at 6 weeks.	0.00% 0/25 • Adverse event data were collected over 8 weeks. The subjects had their baseline test meal at time 0, insulin / placebo was given weeks 2-8, and the second test meal (for calculation of primary endpoint) was at 6 weeks.
Respiratory, thoracic and mediastinal disorders CF pulmonary exacerbation	0.00% 0/12 • Adverse event data were collected over 8 weeks. The subjects had their baseline test meal at time 0, insulin / placebo was given weeks 2-8, and the second test meal (for calculation of primary endpoint) was at 6 weeks.	0.00% 0/13 • Adverse event data were collected over 8 weeks. The subjects had their baseline test meal at time 0, insulin / placebo was given weeks 2-8, and the second test meal (for calculation of primary endpoint) was at 6 weeks.	13.3% 2/15 • Number of events 2 • Adverse event data were collected over 8 weeks. The subjects had their baseline test meal at time 0, insulin / placebo was given weeks 2-8, and the second test meal (for calculation of primary endpoint) was at 6 weeks.	0.00% 0/25 • Adverse event data were collected over 8 weeks. The subjects had their baseline test meal at time 0, insulin / placebo was given weeks 2-8, and the second test meal (for calculation of primary endpoint) was at 6 weeks.
General disorders meal technical problems	8.3% 1/12 • Number of events 1 • Adverse event data were collected over 8 weeks. The subjects had their baseline test meal at time 0, insulin / placebo was given weeks 2-8, and the second test meal (for calculation of primary endpoint) was at 6 weeks.	15.4% 2/13 • Number of events 2 • Adverse event data were collected over 8 weeks. The subjects had their baseline test meal at time 0, insulin / placebo was given weeks 2-8, and the second test meal (for calculation of primary endpoint) was at 6 weeks.	0.00% 0/15 • Adverse event data were collected over 8 weeks. The subjects had their baseline test meal at time 0, insulin / placebo was given weeks 2-8, and the second test meal (for calculation of primary endpoint) was at 6 weeks.	8.0% 2/25 • Number of events 2 • Adverse event data were collected over 8 weeks. The subjects had their baseline test meal at time 0, insulin / placebo was given weeks 2-8, and the second test meal (for calculation of primary endpoint) was at 6 weeks.
Gastrointestinal disorders hyperglycemia	0.00% 0/12 • Adverse event data were collected over 8 weeks. The subjects had their baseline test meal at time 0, insulin / placebo was given weeks 2-8, and the second test meal (for calculation of primary endpoint) was at 6 weeks.	0.00% 0/13 • Adverse event data were collected over 8 weeks. The subjects had their baseline test meal at time 0, insulin / placebo was given weeks 2-8, and the second test meal (for calculation of primary endpoint) was at 6 weeks.	0.00% 0/15 • Adverse event data were collected over 8 weeks. The subjects had their baseline test meal at time 0, insulin / placebo was given weeks 2-8, and the second test meal (for calculation of primary endpoint) was at 6 weeks.	4.0% 1/25 • Number of events 1 • Adverse event data were collected over 8 weeks. The subjects had their baseline test meal at time 0, insulin / placebo was given weeks 2-8, and the second test meal (for calculation of primary endpoint) was at 6 weeks.
General disorders covid center closure	0.00% 0/12 • Adverse event data were collected over 8 weeks. The subjects had their baseline test meal at time 0, insulin / placebo was given weeks 2-8, and the second test meal (for calculation of primary endpoint) was at 6 weeks.	0.00% 0/13 • Adverse event data were collected over 8 weeks. The subjects had their baseline test meal at time 0, insulin / placebo was given weeks 2-8, and the second test meal (for calculation of primary endpoint) was at 6 weeks.	6.7% 1/15 • Number of events 1 • Adverse event data were collected over 8 weeks. The subjects had their baseline test meal at time 0, insulin / placebo was given weeks 2-8, and the second test meal (for calculation of primary endpoint) was at 6 weeks.	0.00% 0/25 • Adverse event data were collected over 8 weeks. The subjects had their baseline test meal at time 0, insulin / placebo was given weeks 2-8, and the second test meal (for calculation of primary endpoint) was at 6 weeks.
General disorders patient withdrawal	0.00% 0/12 • Adverse event data were collected over 8 weeks. The subjects had their baseline test meal at time 0, insulin / placebo was given weeks 2-8, and the second test meal (for calculation of primary endpoint) was at 6 weeks.	0.00% 0/13 • Adverse event data were collected over 8 weeks. The subjects had their baseline test meal at time 0, insulin / placebo was given weeks 2-8, and the second test meal (for calculation of primary endpoint) was at 6 weeks.	6.7% 1/15 • Number of events 1 • Adverse event data were collected over 8 weeks. The subjects had their baseline test meal at time 0, insulin / placebo was given weeks 2-8, and the second test meal (for calculation of primary endpoint) was at 6 weeks.	0.00% 0/25 • Adverse event data were collected over 8 weeks. The subjects had their baseline test meal at time 0, insulin / placebo was given weeks 2-8, and the second test meal (for calculation of primary endpoint) was at 6 weeks.

Additional Information

Antoinette Moran

University of Minnesota

Phone: 612-624-5409

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place