Trial Outcomes & Findings for Effect of Sitagliptin on Short-Term Metabolic Dysregulation of Oral Glucocorticoid Therapy (NCT NCT01488279)

NCT ID: NCT01488279

Last Updated: 2018-03-12

Results Overview

Insulin Sensitivity measured at the end of each treatment period. The primary outcome variable was the difference in the disposition index (DI) determined as the product of the acute insulin response to glucose (AIRg) x the insulin sensitivity index (SI) in subjects during IVGTT on the 8th day (after 7 days) of on dex + placebo, then a after a washout of approximately 4 weeks, participants crossed over to dex + sitagliptin 100 mg x 7 days. Subjects were randomized to order of medication. The primary analyses will be an ANCOVA, including baseline responses as a covariate.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

10 participants

Primary outcome timeframe

Measured on day #8 (after 8 days of sitagliptin or placebo) followed by a 4 week washout then measured again on day #8 (after 8 days of crossover treatment).

Results posted on

2018-03-12

Participant Flow

Participant milestones

Participant milestones
Measure
Sitagliptin, Then Placebo
Dex 2.5 mg + sitagliptin 100 mg daily (7 days), washout (4-6 weeks), dex + placebo (7 days)
Placebo, Then Sitaglipton
Dex 2.5 mg + placebo (7 days), washout (4-6 weeks), Sitalgiptin + placebo ( 7 days)
Overall Study
STARTED
5
5
Overall Study
COMPLETED
5
5
Overall Study
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effect of Sitagliptin on Short-Term Metabolic Dysregulation of Oral Glucocorticoid Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Sitagliptin, Then Placebo
n=5 Participants
This arm involves randomization to dexamethasone 2.5 mg + sitagliptin 100 mg daily x 7 days followed by MTT and IVGTT on subsequent days. There was a 4-6 week washout, then subjects crossed over to dex + placebo.
Placebo, Then Sitagliptin
n=5 Participants
This arm involves randomization to dexamethasone 2.5 mg orally + placebo x 7 days followed by MTT and IVGTT on subsequent days. There was a 4-6 weeks washout, then subjects crossed over to dex + sitagliptin.
Total
n=10 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=93 Participants
0 Participants
n=4 Participants
0 Participants
n=27 Participants
Age, Categorical
Between 18 and 65 years
5 Participants
n=93 Participants
5 Participants
n=4 Participants
10 Participants
n=27 Participants
Age, Categorical
>=65 years
0 Participants
n=93 Participants
0 Participants
n=4 Participants
0 Participants
n=27 Participants
Age, Continuous
52.5 years
STANDARD_DEVIATION 5.5 • n=93 Participants
52.5 years
STANDARD_DEVIATION 5.5 • n=4 Participants
52.5 years
STANDARD_DEVIATION 5.5 • n=27 Participants
Sex: Female, Male
Female
3 Participants
n=93 Participants
3 Participants
n=4 Participants
6 Participants
n=27 Participants
Sex: Female, Male
Male
2 Participants
n=93 Participants
2 Participants
n=4 Participants
4 Participants
n=27 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
n=93 Participants
0 Participants
n=4 Participants
0 Participants
n=27 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
5 Participants
n=93 Participants
5 Participants
n=4 Participants
10 Participants
n=27 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=93 Participants
0 Participants
n=4 Participants
0 Participants
n=27 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=93 Participants
0 Participants
n=4 Participants
0 Participants
n=27 Participants
Race (NIH/OMB)
Asian
0 Participants
n=93 Participants
0 Participants
n=4 Participants
0 Participants
n=27 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=93 Participants
0 Participants
n=4 Participants
0 Participants
n=27 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=93 Participants
0 Participants
n=4 Participants
0 Participants
n=27 Participants
Race (NIH/OMB)
White
5 Participants
n=93 Participants
5 Participants
n=4 Participants
10 Participants
n=27 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=93 Participants
0 Participants
n=4 Participants
0 Participants
n=27 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=93 Participants
0 Participants
n=4 Participants
0 Participants
n=27 Participants
Region of Enrollment
United States
5 participants
n=93 Participants
5 participants
n=4 Participants
10 participants
n=27 Participants

PRIMARY outcome

Timeframe: Measured on day #8 (after 8 days of sitagliptin or placebo) followed by a 4 week washout then measured again on day #8 (after 8 days of crossover treatment).

Population: Subjects were randomized to the order to study medication (dex + sitagliptin vs dex + placebo) by the pharmacy in order to keep double blinding

Insulin Sensitivity measured at the end of each treatment period. The primary outcome variable was the difference in the disposition index (DI) determined as the product of the acute insulin response to glucose (AIRg) x the insulin sensitivity index (SI) in subjects during IVGTT on the 8th day (after 7 days) of on dex + placebo, then a after a washout of approximately 4 weeks, participants crossed over to dex + sitagliptin 100 mg x 7 days. Subjects were randomized to order of medication. The primary analyses will be an ANCOVA, including baseline responses as a covariate.

Outcome measures

Outcome measures
Measure
Sitagliptin
n=10 Participants
This arm involves randomization to dexamethasone 2.5 mg + sitagliptin 100 mg daily x 7 days followed by MTT and IVGTT on subsequent days.
Placebo
n=10 Participants
This arm involves randomization to dexamethasone 2.5 mg orally + placebo x 7 days followed by MTT and IVGTT on subsequent days.
Insulin Sensitivity
1835.4 ratio without units
Standard Error 340.0
1846.0 ratio without units
Standard Error 340.0

SECONDARY outcome

Timeframe: Active GIP would have been measured during MTT after 1 week of dex + sitagliptin and again after 1 week of dex + placebo, but we did not measure active GIP

Population: We did not measure GIP

We had planned to measure the difference or change in active GIP in response to the MTT between the 2 study drug periods: on sitagliptin versus on placebo. However, when other measures were negative, we opted not to pursue this lab assay for cost and time. We did not perform measures of GIP.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Active GLP-1 would have been measured during MTT after 1 week of dex + sitagliptin and again after 1 week of dex + placebo, but we did not measure active GLP-1

Population: We did not measure GLP-1

As with GIP, we had planned to measure the difference or change in active GLP-1 in response to the MTT between the 2 study drug periods: on sitagliptin versus on placebo. We had hypothesized that GIP and GLP-1 would be elevated while on the DPP4 inhibitor compared to placebo as this is the mechanism of action of the drug sitagliptin. When other measures were negative, we elected not to pursue this due to time and cost.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: measured on day #9 (after 7 days of study drug and 1 day of IVGTT) of sitagliptin during MTT, then after 4 week washout, measured again on day #9 (after 7 days of study drug + 1 day of IVGTT) of dex + placebo during MTT

Change in glucose response during the MTT. This was the Si (insulin sensitivity). We sought to determine whether there was an improvement in the glucose response after a meal on the DPP4i compared to placebo in the face of steroid (dexamethasone).

Outcome measures

Outcome measures
Measure
Sitagliptin
n=10 Participants
This arm involves randomization to dexamethasone 2.5 mg + sitagliptin 100 mg daily x 7 days followed by MTT and IVGTT on subsequent days.
Placebo
n=10 Participants
This arm involves randomization to dexamethasone 2.5 mg orally + placebo x 7 days followed by MTT and IVGTT on subsequent days.
Change in Glucose Response
4.219 response x 10000 / minute / microUnit/ml
Standard Error 1.368
4.228 response x 10000 / minute / microUnit/ml
Standard Error 1.368

SECONDARY outcome

Timeframe: measured twice: on day #8 (after 7 days of study drug and 1 day of IVGTT) of sitagliptin during MTT, then after 4 week washout, measured again on day #8 (after 7 days of study drug + 1 day of IVGTT) of dex + placebo during MTT

We measured the change in insulin secretion (AIRg or acute insulinogenic response to glucose) during the MTT and compared the insulin secretion on the DPP4 inhibitor (sitagliptin) compared to placebo. We had expected the AIRg to be greater with DPP4i compared to placebo.

Outcome measures

Outcome measures
Measure
Sitagliptin
n=10 Participants
This arm involves randomization to dexamethasone 2.5 mg + sitagliptin 100 mg daily x 7 days followed by MTT and IVGTT on subsequent days.
Placebo
n=10 Participants
This arm involves randomization to dexamethasone 2.5 mg orally + placebo x 7 days followed by MTT and IVGTT on subsequent days.
Change in Insulin Secretion (AIRg or Acute Insulinogenic Response to Glucose)
519.6 pmol/l
Standard Error 0.460
558.6 pmol/l
Standard Error 35.3

Adverse Events

Sitagliptin, Then Placebo

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Placebo, Then Sitagliptin

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Annis Marney

Frist Clinic Endocrinology

Phone: 615-403-8398

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: LTE60