Trial Outcomes & Findings for Mifepristone Effects on Glucose Intolerance in Obese/Overweight Adults (NCT NCT01419535)
NCT ID: NCT01419535
Last Updated: 2021-04-14
Results Overview
insulin sensitivity index based on the effect of insulin on glucose during frequently sampled intravenous glucose tolerance test (FSIVGTT)
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
19 participants
Primary outcome timeframe
Nine days
Results posted on
2021-04-14
Participant Flow
Subjects were recruited to the study by advertisements and fliers. Sixty-three adults were evaluated at the single study site (the NIH Clinical Center) after providing informed consent. The first subject consented on November 11, 2011 and the final subject consented on April 16, 2015.
Forty-four subjects were excluded; 31 had a normal oral glucose tolerance test and fasting glucose level, 2 exceeded BMI criterion, 2 exceeded HbA1C criterion, 2 had depression, and seven subjects had one of the following exclusion criteria: required insulin, \<35 years old, memory problems/compliance, abnormal thyroid function, drop out after screening, abnormal late night salivary cortisol, failure to complete screening. The remaining 19 subjects were randomized.
Participant milestones
| Measure |
Mifepristone, Then Placebo
Participants first received Mifepristone 50mg tablet every six hours for nine days. After a washout period of no fewer than 6 but no more than 8 weeks, they then received Placebo tablet (matching mifepristone 50 mg) every six hours for nine days.
Mifepristone: Mifepristone 50mg tablet by mouth every six hours for nine days.
Placebo: Placebo (matching mifepristone 50mg tablet) by mouth every six hours for nine days.
|
Placebo, Then Mifepristone
Participants first received Placebo tablet (matching mifepristone 50 mg) every six hours for nine days. After a washout period of no fewer than 6 but no more than 8 weeks, they then received Mifepristone 50 mg tablet every six hours for nine days.
Mifepristone: Mifepristone 50mg tablet by mouth every six hours for nine days.
Placebo: Placebo (matching mifepristone 50mg tablet) by mouth every six hours for nine days.
|
|---|---|---|
|
Overall Study
STARTED
|
9
|
10
|
|
Overall Study
COMPLETED
|
8
|
8
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
Reasons for withdrawal
| Measure |
Mifepristone, Then Placebo
Participants first received Mifepristone 50mg tablet every six hours for nine days. After a washout period of no fewer than 6 but no more than 8 weeks, they then received Placebo tablet (matching mifepristone 50 mg) every six hours for nine days.
Mifepristone: Mifepristone 50mg tablet by mouth every six hours for nine days.
Placebo: Placebo (matching mifepristone 50mg tablet) by mouth every six hours for nine days.
|
Placebo, Then Mifepristone
Participants first received Placebo tablet (matching mifepristone 50 mg) every six hours for nine days. After a washout period of no fewer than 6 but no more than 8 weeks, they then received Mifepristone 50 mg tablet every six hours for nine days.
Mifepristone: Mifepristone 50mg tablet by mouth every six hours for nine days.
Placebo: Placebo (matching mifepristone 50mg tablet) by mouth every six hours for nine days.
|
|---|---|---|
|
Overall Study
could not maintain iv line
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
Mifepristone Effects on Glucose Intolerance in Obese/Overweight Adults
Baseline characteristics by cohort
| Measure |
Mifepristone, Then Placebo
n=8 Participants
Participants first received Mifepristone 50mg tablet every six hours for nine days. After a washout period of no fewer than 6 but no more than 8 weeks, they then received Placebo tablet (matching mifepristone 50 mg) every six hours for nine days.
Mifepristone: Mifepristone 50mg tablet by mouth every six hours for nine days.
Placebo: Placebo (matching mifepristone 50mg tablet) by mouth every six hours for nine days.
|
Placebo, Then Mifepristone
n=8 Participants
Participants first received Placebo tablet (matching mifepristone 50 mg) every six hours for nine days. After a washout period of no fewer than 6 but no more than 8 weeks, they then received Mifepristone 50 mg tablet every six hours for nine days.
Mifepristone: Mifepristone 50mg tablet by mouth every six hours for nine days.
Placebo: Placebo (matching mifepristone 50mg tablet) by mouth every six hours for nine days.
|
Total
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
7 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 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
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Age, Continuous
|
56.6 years
STANDARD_DEVIATION 6.5 • n=5 Participants
|
52.8 years
STANDARD_DEVIATION 8.9 • n=7 Participants
|
54.7 years
STANDARD_DEVIATION 7.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
8 participants
n=5 Participants
|
8 participants
n=7 Participants
|
16 participants
n=5 Participants
|
|
Weight
|
92.8 kg
STANDARD_DEVIATION 15.8 • n=5 Participants
|
102 kg
STANDARD_DEVIATION 15.9 • n=7 Participants
|
97.2 kg
STANDARD_DEVIATION 16.0 • n=5 Participants
|
|
Body mass index
|
30.8 kg/M^2
STANDARD_DEVIATION 4.12 • n=5 Participants
|
34.0 kg/M^2
STANDARD_DEVIATION 2.37 • n=7 Participants
|
32.4 kg/M^2
STANDARD_DEVIATION 4.12 • n=5 Participants
|
|
systolic blood pressure
|
124 mmHg
STANDARD_DEVIATION 16.1 • n=5 Participants
|
133 mmHg
STANDARD_DEVIATION 10.5 • n=7 Participants
|
128 mmHg
STANDARD_DEVIATION 13.9 • n=5 Participants
|
|
diastolic blood pressure
|
77.6 mmHg
STANDARD_DEVIATION 4.7 • n=5 Participants
|
76.9 mmHg
STANDARD_DEVIATION 9.9 • n=7 Participants
|
77.3 mmHg
STANDARD_DEVIATION 7.5 • n=5 Participants
|
|
total cholesterol
|
177.9 mg/dL
STANDARD_DEVIATION 59.0 • n=5 Participants
|
184.3 mg/dL
STANDARD_DEVIATION 53.8 • n=7 Participants
|
181.1 mg/dL
STANDARD_DEVIATION 54.6 • n=5 Participants
|
|
HDL cholesterol
|
51.1 mg/dL
STANDARD_DEVIATION 7.5 • n=5 Participants
|
40.0 mg/dL
STANDARD_DEVIATION 8.6 • n=7 Participants
|
45.6 mg/dL
STANDARD_DEVIATION 9.7 • n=5 Participants
|
|
LDL cholesterol
|
104.9 mg/dL
STANDARD_DEVIATION 41.3 • n=5 Participants
|
108.3 mg/dL
STANDARD_DEVIATION 41.0 • n=7 Participants
|
106.6 mg/dL
STANDARD_DEVIATION 40.1 • n=5 Participants
|
|
triglycerides
|
108.8 mg/dL
STANDARD_DEVIATION 88.3 • n=5 Participants
|
180.0 mg/dL
STANDARD_DEVIATION 92.3 • n=7 Participants
|
144.4 mg/dL
STANDARD_DEVIATION 94.7 • n=5 Participants
|
|
free fatty acids
|
0.62 mg/dL
STANDARD_DEVIATION 0.18 • n=5 Participants
|
0.54 mg/dL
STANDARD_DEVIATION 0.23 • n=7 Participants
|
0.60 mg/dL
STANDARD_DEVIATION 0.19 • n=5 Participants
|
|
fasting glucose
|
101.0 mg/dL
STANDARD_DEVIATION 5.8 • n=5 Participants
|
108.1 mg/dL
STANDARD_DEVIATION 20.6 • n=7 Participants
|
104.6 mg/dL
STANDARD_DEVIATION 15.0 • n=5 Participants
|
|
fasting insulin
|
75.7 pmol/L
STANDARD_DEVIATION 35.4 • n=5 Participants
|
143.1 pmol/L
STANDARD_DEVIATION 43.3 • n=7 Participants
|
109 pmol/L
STANDARD_DEVIATION 51.8 • n=5 Participants
|
|
A1C
|
5.9 percent
STANDARD_DEVIATION 0.35 • n=5 Participants
|
6.3 percent
STANDARD_DEVIATION 0.49 • n=7 Participants
|
6.1 percent
STANDARD_DEVIATION 0.45 • n=5 Participants
|
|
Urine free cortisol
|
27.8 ug/dl
STANDARD_DEVIATION 23.0 • n=5 Participants
|
18.1 ug/dl
STANDARD_DEVIATION 7.2 • n=7 Participants
|
22.9 ug/dl
STANDARD_DEVIATION 17.2 • n=5 Participants
|
PRIMARY outcome
Timeframe: Nine daysPopulation: 2 subjects in each group missing data due to iv line problems
insulin sensitivity index based on the effect of insulin on glucose during frequently sampled intravenous glucose tolerance test (FSIVGTT)
Outcome measures
| Measure |
Post-mifepristone
n=16 Participants
All subjects tested after mifepristone administration, compared to baseline
|
Post-placebo
n=16 Participants
all subjects tested after placebo administration, compared to baseline
|
|---|---|---|
|
Change in Insulin Sensitivity Index
|
1.49 min-1·μU·ml-1
Standard Deviation 1.17
|
1.41 min-1·μU·ml-1
Standard Deviation 0.87
|
SECONDARY outcome
Timeframe: Nine daysfasting plasma glucose after study agent compared to baseline
Outcome measures
| Measure |
Post-mifepristone
n=16 Participants
All subjects tested after mifepristone administration, compared to baseline
|
Post-placebo
n=16 Participants
all subjects tested after placebo administration, compared to baseline
|
|---|---|---|
|
Change in Fasting Plasma Glucose
|
100.4 mg/dL
Standard Error 5.3
|
107.8 mg/dL
Standard Error 15.7
|
SECONDARY outcome
Timeframe: 9 daysFasting insulin after study agent administration compared to baseline
Outcome measures
| Measure |
Post-mifepristone
n=16 Participants
All subjects tested after mifepristone administration, compared to baseline
|
Post-placebo
n=16 Participants
all subjects tested after placebo administration, compared to baseline
|
|---|---|---|
|
Change in Fasting Insulin Levels
|
95.6 pmol/L
Standard Deviation 76.1
|
142.8 pmol/L
Standard Deviation 102.2
|
SECONDARY outcome
Timeframe: 9 daysHOMA-IR is an index of insulin resistance, measured as glucose in mmol/L x insulin in mIU/mL)/22.5. HOMA-IR \> 2.5 indicates insulin resistance.
Outcome measures
| Measure |
Post-mifepristone
n=16 Participants
All subjects tested after mifepristone administration, compared to baseline
|
Post-placebo
n=16 Participants
all subjects tested after placebo administration, compared to baseline
|
|---|---|---|
|
Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
|
3.58 units on a scale
Standard Deviation 3.27
|
5.78 units on a scale
Standard Deviation 4.92
|
SECONDARY outcome
Timeframe: 9 daysThe adipose tissue insulin resistance index (Adipo-IR), a surrogate measure for fasting adipose-tissue insulin resistance, was calculated as the product of fasting insulin and fasting free fatty acids (FFA)
Outcome measures
| Measure |
Post-mifepristone
n=16 Participants
All subjects tested after mifepristone administration, compared to baseline
|
Post-placebo
n=16 Participants
all subjects tested after placebo administration, compared to baseline
|
|---|---|---|
|
Adipose-tissue Insulin Resistance Index (Adipo-IR)
|
49.9 mmol/l·μU/l
Standard Deviation 45.9
|
65.5 mmol/l·μU/l
Standard Deviation 43.8
|
SECONDARY outcome
Timeframe: 9 daysThe Adipo-SI was calculated as ratio of the slope of the linear decrease in natural log transformed FFA \[Ln (FFA) slope\] during the first 90 minutes of the FSIVGTT and the area under the curve (AUC) of insulin during that 90-minute period (AUC Insulin 0-90 min).
Outcome measures
| Measure |
Post-mifepristone
n=16 Participants
All subjects tested after mifepristone administration, compared to baseline
|
Post-placebo
n=16 Participants
all subjects tested after placebo administration, compared to baseline
|
|---|---|---|
|
Adipose-tissue Insulin Sensitivity Index (Adipo-SI)
|
61.7 ln(mmol /uU/mL*min)*10^8
Standard Deviation 32.9
|
42.8 ln(mmol /uU/mL*min)*10^8
Standard Deviation 23.9
|
Adverse Events
Post-mifepristone
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Post-placebo
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Post-mifepristone
n=16 participants at risk
All subjects tested after mifepristone administration, compared to baseline
|
Post-placebo
n=16 participants at risk
all subjects tested after placebo administration, compared to baseline
|
|---|---|---|
|
Hepatobiliary disorders
abnormal blood chemistry
|
0.00%
0/16 • Subjects returned for safety labs and discussion of any adverse events on approximately day 19 and day 33 after discontinuation of study agents.
|
12.5%
2/16 • Number of events 2 • Subjects returned for safety labs and discussion of any adverse events on approximately day 19 and day 33 after discontinuation of study agents.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place