Trial Outcomes & Findings for Endogenous Opioid Activity and Affective State in Insulin Resistant Women (NCT NCT02069379)
NCT ID: NCT02069379
Last Updated: 2018-11-08
Results Overview
Mu-opioid neurotransmission in limbic brain regions at baseline and change from baseline after metformin treatment
COMPLETED
PHASE4
42 participants
Baseline, 20 weeks, 40 weeks
2018-11-08
Participant Flow
Participant milestones
| Measure |
Controls
metabolically healthy controls will participate in baseline assessments only, and will not be randomized to the placebo and metformin treatment arms.
|
Insulin Resistant Participants (Placebo First)
Women classified as insulin resistant will participate in both a placebo and a metformin treatment arm, each lasting about 16 weeks. Women will be randomized to order of treatment arms.
|
Insulin Resistant Participants (Metformin First)
Women classified as insulin resistant and randomized to Metformin treatment arm 1st and Placebo treatment arm 2nd
|
Insulin Resistant (Not Randomized)
Insulin resistant participants not randomized to treatment arms
|
|---|---|---|---|---|
|
Baseline Measurements
STARTED
|
30
|
4
|
2
|
6
|
|
Baseline Measurements
Baseline Measurements Taken
|
30
|
4
|
2
|
6
|
|
Baseline Measurements
COMPLETED
|
27
|
4
|
2
|
4
|
|
Baseline Measurements
NOT COMPLETED
|
3
|
0
|
0
|
2
|
|
First Treatment Arm
STARTED
|
0
|
4
|
2
|
0
|
|
First Treatment Arm
COMPLETED
|
0
|
3
|
1
|
0
|
|
First Treatment Arm
NOT COMPLETED
|
0
|
1
|
1
|
0
|
|
Washout Period (4 Weeks)
STARTED
|
0
|
3
|
1
|
0
|
|
Washout Period (4 Weeks)
COMPLETED
|
0
|
1
|
1
|
0
|
|
Washout Period (4 Weeks)
NOT COMPLETED
|
0
|
2
|
0
|
0
|
|
Second Treatment Arm
STARTED
|
0
|
1
|
1
|
0
|
|
Second Treatment Arm
COMPLETED
|
0
|
1
|
0
|
0
|
|
Second Treatment Arm
NOT COMPLETED
|
0
|
0
|
1
|
0
|
Reasons for withdrawal
| Measure |
Controls
metabolically healthy controls will participate in baseline assessments only, and will not be randomized to the placebo and metformin treatment arms.
|
Insulin Resistant Participants (Placebo First)
Women classified as insulin resistant will participate in both a placebo and a metformin treatment arm, each lasting about 16 weeks. Women will be randomized to order of treatment arms.
|
Insulin Resistant Participants (Metformin First)
Women classified as insulin resistant and randomized to Metformin treatment arm 1st and Placebo treatment arm 2nd
|
Insulin Resistant (Not Randomized)
Insulin resistant participants not randomized to treatment arms
|
|---|---|---|---|---|
|
Baseline Measurements
Lost to Follow-up
|
1
|
0
|
0
|
0
|
|
Baseline Measurements
Ineligible based on initial assessments
|
2
|
0
|
0
|
2
|
|
First Treatment Arm
Lost to Follow-up
|
0
|
1
|
1
|
0
|
|
Washout Period (4 Weeks)
Lost to Follow-up
|
0
|
1
|
0
|
0
|
|
Washout Period (4 Weeks)
Unrelated event
|
0
|
1
|
0
|
0
|
|
Second Treatment Arm
Lost to Follow-up
|
0
|
0
|
1
|
0
|
Baseline Characteristics
Endogenous Opioid Activity and Affective State in Insulin Resistant Women
Baseline characteristics by cohort
| Measure |
Controls
n=30 Participants
metabolically healthy controls will participate in baseline assessments only, and will not be randomized to the placebo and metformin treatment arms.
|
Insulin Resistant Participants
n=12 Participants
Women classified as insulin resistant will participate in both a placebo and a metformin treatment arm, each lasting about 16 weeks. Women will be randomized to order of treatment arms.
|
Total
n=42 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
30 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
42 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
30 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
42 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
30 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
42 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
6 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
9 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
|
7 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
13 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
30 participants
n=5 Participants
|
12 participants
n=7 Participants
|
42 participants
n=5 Participants
|
|
Glucose
|
80.29 mg/dL
STANDARD_DEVIATION 5.33 • n=5 Participants
|
84.67 mg/dL
STANDARD_DEVIATION 9.99 • n=7 Participants
|
81.60 mg/dL
STANDARD_DEVIATION 7.21 • n=5 Participants
|
|
Plasma Insulin Levels
|
10.18 mIU/L
STANDARD_DEVIATION 1.99 • n=5 Participants
|
18.61 mIU/L
STANDARD_DEVIATION 3.36 • n=7 Participants
|
12.71 mIU/L
STANDARD_DEVIATION 4.61 • n=5 Participants
|
|
HOMA Insulin Resistance (IR)
|
2.01 HOMA IR
STANDARD_DEVIATION 0.42 • n=5 Participants
|
3.94 HOMA IR
STANDARD_DEVIATION 1.11 • n=7 Participants
|
2.56 HOMA IR
STANDARD_DEVIATION 1.12 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, 20 weeks, 40 weeksPopulation: PET scanners available were replaced for other institutional reasons which resulted in image production so incompatible as to be not comparable. Therefore PET image data files were unable to be analyzed due to inconsistencies with imaging techniques.
Mu-opioid neurotransmission in limbic brain regions at baseline and change from baseline after metformin treatment
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Baseline, 20 weeks, 40 weeksPopulation: PET scanners available were replaced for other institutional reasons which resulted in image production so incompatible as to be not comparable. Therefore PET image data files were unable to be analyzed due to inconsistencies with imaging techniques.
Mu-opioid neurotransmission in limbic brain regions at baseline and change from baseline after metformin treatment
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Baseline, 20 weeks, 40 weeksPopulation: PET scanners available were replaced for other institutional reasons which resulted in image production so incompatible as to be not comparable. Therefore PET image data files were unable to be analyzed due to inconsistencies with imaging techniques.
Mu-opioid neurotransmission in limbic regions at baseline and change from baseline after metformin treatment
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Baseline, 20 weeks, 40 weeksPopulation: PET scanners available were replaced for other institutional reasons which resulted in image production so incompatible as to be not comparable. Therefore PET image data files were unable to be analyzed due to inconsistencies with imaging techniques.
Mu-opioid neurotransmission in limbic brain regions at baseline and change from baseline after metformin treatment
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: BaselinePopulation: All women assessed at baseline, prior to treatment arm randomization, so all insulin resistant women are analyzed as a single group. On the Control side, one woman's data for affective state is unavailable.
Compare positive affective state between controls and insulin resistant women. Positive and Negative Affect Schedule - positive affective state. Scores can range from 10-50, with higher scores representing more positive affective state (better outcome)
Outcome measures
| Measure |
Controls
n=26 Participants
metabolically healthy controls will participate in baseline assessments only, and will not be randomized to the placebo and metformin treatment arms.
|
Metformin
n=12 Participants
16 weeks treatment with metformin (insulin sensitizing treatment)
Metformin: Women classified as insulin resistant will participate in both a placebo and a metformin treatment arm, each lasting about 16 weeks. Women will be randomized to order of treatment arms.
|
Placebo
Placebo comparator to metformin treatment
Placebo: Placebo capsules prepared identically to Metformin capsules
|
|---|---|---|---|
|
Positive and Negative Affect Schedule - Positive Affective State
|
28.23 units on a scale
Standard Deviation 8.29
|
21.83 units on a scale
Standard Deviation 8.84
|
—
|
SECONDARY outcome
Timeframe: BaselinePopulation: All women assessed at baseline, prior to treatment arm randomization, so all insulin resistant women analyzed as a single group. One woman's baseline affective score is not available.
Measure of overall negative affective state at baseline in controls and insulin resistant women. Positive and Negative Affect Schedule - negative affective state. Scores can range from 10-50, with higher scores representing more negative affective state (worse outcome)
Outcome measures
| Measure |
Controls
n=26 Participants
metabolically healthy controls will participate in baseline assessments only, and will not be randomized to the placebo and metformin treatment arms.
|
Metformin
n=12 Participants
16 weeks treatment with metformin (insulin sensitizing treatment)
Metformin: Women classified as insulin resistant will participate in both a placebo and a metformin treatment arm, each lasting about 16 weeks. Women will be randomized to order of treatment arms.
|
Placebo
Placebo comparator to metformin treatment
Placebo: Placebo capsules prepared identically to Metformin capsules
|
|---|---|---|---|
|
Positive and Negative Affect Schedule - Negative Affective State
|
11.46 units on a scale
Standard Deviation 1.68
|
12.83 units on a scale
Standard Deviation 6.74
|
—
|
SECONDARY outcome
Timeframe: BaselinePopulation: All women assessed at baseline, prior to treatment arm randomization, so all insulin resistant women analyzed as a single group; one woman on the control side's data is not available
Measure of overall negative mood at baseline in controls and insulin resistant women; Profile of Mood States are standardized to a relative score where a higher score is a worse mood state. Standardized cores generally ranged from - 11 to 52.
Outcome measures
| Measure |
Controls
n=26 Participants
metabolically healthy controls will participate in baseline assessments only, and will not be randomized to the placebo and metformin treatment arms.
|
Metformin
n=12 Participants
16 weeks treatment with metformin (insulin sensitizing treatment)
Metformin: Women classified as insulin resistant will participate in both a placebo and a metformin treatment arm, each lasting about 16 weeks. Women will be randomized to order of treatment arms.
|
Placebo
Placebo comparator to metformin treatment
Placebo: Placebo capsules prepared identically to Metformin capsules
|
|---|---|---|---|
|
Profile of Mood States - Overall Negative Mood
|
3.15 units on a scale
Standard Deviation 10.60
|
14.42 units on a scale
Standard Deviation 20.35
|
—
|
SECONDARY outcome
Timeframe: BaselinePopulation: All women assessed at baseline, prior to treatment arm randomization, so all insulin resistant women analyzed as a single group. The data for one woman in the control group is unavailable. Note: women with BDI scores of greater than 20 were excluded from the study by definition and therefore could not be in either arm.
Measure of depression symptoms at baseline in controls and insulin resistant women. The Beck Depression Index runs on a scale from 0 to 63 where low scores mean less depression and high scores mean greater depression. Clinically, scores of 14 or higher are considered mild depression; 20 is moderate and 29 is severe.
Outcome measures
| Measure |
Controls
n=26 Participants
metabolically healthy controls will participate in baseline assessments only, and will not be randomized to the placebo and metformin treatment arms.
|
Metformin
n=12 Participants
16 weeks treatment with metformin (insulin sensitizing treatment)
Metformin: Women classified as insulin resistant will participate in both a placebo and a metformin treatment arm, each lasting about 16 weeks. Women will be randomized to order of treatment arms.
|
Placebo
Placebo comparator to metformin treatment
Placebo: Placebo capsules prepared identically to Metformin capsules
|
|---|---|---|---|
|
Beck Depression Index
|
2.93 units on a scale
Standard Deviation 4.36
|
7.00 units on a scale
Standard Deviation 9.96
|
—
|
Adverse Events
Controls
Placebo (First Assignment & Washout or Second Assignment)
Metformin (First Assignment & Washout or Second Assignment)
Insulin-resistant Women Not Randomized
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Controls
n=30 participants at risk
metabolically healthy controls will participate in baseline assessments only, and will not be randomized to the placebo and metformin treatment arms.
|
Placebo (First Assignment & Washout or Second Assignment)
n=5 participants at risk
Placebo comparator to metformin treatment
Placebo: Placebo capsules prepared identically to Metformin capsules
|
Metformin (First Assignment & Washout or Second Assignment)
n=3 participants at risk
16 weeks treatment with metformin (insulin sensitizing treatment)
Metformin: Women classified as insulin resistant will participate in both a placebo and a metformin treatment arm, each lasting about 16 weeks. Women will be randomized to order of treatment arms.
|
Insulin-resistant Women Not Randomized
n=6 participants at risk
These participants, like controls, did not continue beyond baseline and were not assigned any metformin or placebo.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Nausea?
|
3.3%
1/30 • Number of events 1 • Adverse event data were collected for up to 40 weeks of study participation.
|
0.00%
0/5 • Adverse event data were collected for up to 40 weeks of study participation.
|
0.00%
0/3 • Adverse event data were collected for up to 40 weeks of study participation.
|
0.00%
0/6 • Adverse event data were collected for up to 40 weeks of study participation.
|
|
Renal and urinary disorders
Elevated potassium levels
|
3.3%
1/30 • Number of events 1 • Adverse event data were collected for up to 40 weeks of study participation.
|
0.00%
0/5 • Adverse event data were collected for up to 40 weeks of study participation.
|
0.00%
0/3 • Adverse event data were collected for up to 40 weeks of study participation.
|
0.00%
0/6 • Adverse event data were collected for up to 40 weeks of study participation.
|
|
Nervous system disorders
Self-reported seizure
|
0.00%
0/30 • Adverse event data were collected for up to 40 weeks of study participation.
|
20.0%
1/5 • Number of events 1 • Adverse event data were collected for up to 40 weeks of study participation.
|
0.00%
0/3 • Adverse event data were collected for up to 40 weeks of study participation.
|
0.00%
0/6 • Adverse event data were collected for up to 40 weeks of study participation.
|
|
Nervous system disorders
Brain lesion detected
|
0.00%
0/30 • Adverse event data were collected for up to 40 weeks of study participation.
|
20.0%
1/5 • Number of events 1 • Adverse event data were collected for up to 40 weeks of study participation.
|
0.00%
0/3 • Adverse event data were collected for up to 40 weeks of study participation.
|
0.00%
0/6 • Adverse event data were collected for up to 40 weeks of study participation.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place