Trial Outcomes & Findings for Pharmacogenomics of Thiazolidinediones (NCT NCT01135394)
NCT ID: NCT01135394
Last Updated: 2024-03-15
Results Overview
Change in insulin resistance was calculated as change (end of treatment minus baseline) in HOMA-IR index (glucose (mg/dL) x insulin (μU/mL)/405)
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
114 participants
Primary outcome timeframe
12 weeks
Results posted on
2024-03-15
Participant Flow
Recruitment was through advertisements in local publications and bulletin boards in the University of Maryland and Baltimore area. Additional recruitment among the Old Order Amish was through the University of Maryland Amish Research Clinic in Lancaster County, Pennsylvania.
Screening assessments done following informed consent include anthropometry, screening bloodwork, medical history and baseline study assessments. Participants may be excluded prior to start of study drug and/or baseline assessments if they do not meet eligibility criteria.
Participant milestones
| Measure |
Pioglitazone (Actos)
Participants will have metabolism studies to consist of outpatient X-ray and magnetic resonance (MR) measurements of bone density and body composition, metabolic testing (intravenous glucose tolerance test), and muscle and adipose tissue biopsies. Blood will also be drawn for genetic testing and for microarray studies of leukocytes. Upon completion of the above studies, the participant will begin pioglitazone therapy. Every 4 weeks throughout the drug intervention, glycemic control, lipoprotein profile, and weight will be monitored. After 12 weeks of pioglitazone therapy, the X-ray and MR measurements of body composition, the biopsies, microarray studies for leukocytes and the metabolic tests will be repeated.
Pioglitazone: 30 mg tablet once daily for 4 weeks, then increased to 45 mg once daily for an additional 8 weeks. Total dosage period is 12 weeks.
|
|---|---|
|
Screening
STARTED
|
114
|
|
Screening
COMPLETED
|
81
|
|
Screening
NOT COMPLETED
|
33
|
|
Baseline Assessment
STARTED
|
81
|
|
Baseline Assessment
COMPLETED
|
66
|
|
Baseline Assessment
NOT COMPLETED
|
15
|
|
Study Treatment
STARTED
|
66
|
|
Study Treatment
COMPLETED
|
62
|
|
Study Treatment
NOT COMPLETED
|
4
|
Reasons for withdrawal
| Measure |
Pioglitazone (Actos)
Participants will have metabolism studies to consist of outpatient X-ray and magnetic resonance (MR) measurements of bone density and body composition, metabolic testing (intravenous glucose tolerance test), and muscle and adipose tissue biopsies. Blood will also be drawn for genetic testing and for microarray studies of leukocytes. Upon completion of the above studies, the participant will begin pioglitazone therapy. Every 4 weeks throughout the drug intervention, glycemic control, lipoprotein profile, and weight will be monitored. After 12 weeks of pioglitazone therapy, the X-ray and MR measurements of body composition, the biopsies, microarray studies for leukocytes and the metabolic tests will be repeated.
Pioglitazone: 30 mg tablet once daily for 4 weeks, then increased to 45 mg once daily for an additional 8 weeks. Total dosage period is 12 weeks.
|
|---|---|
|
Screening
Lost to Follow-up
|
2
|
|
Screening
Withdrawal by Subject
|
10
|
|
Screening
Screening failure
|
16
|
|
Screening
Physician Decision
|
5
|
|
Baseline Assessment
Withdrawal by Subject
|
9
|
|
Baseline Assessment
Physician Decision
|
3
|
|
Baseline Assessment
Lost to Follow-up
|
2
|
|
Baseline Assessment
Adverse Event
|
1
|
|
Study Treatment
Withdrawal by Subject
|
1
|
|
Study Treatment
Physician Decision
|
1
|
|
Study Treatment
Adverse Event
|
2
|
Baseline Characteristics
HOMA-IR index was calculated only on subjects who had complete data including both intravenous glucose tolerance tests
Baseline characteristics by cohort
| Measure |
Pioglitazone (Actos)
n=114 Participants
Participants will have metabolism studies to consist of outpatient X-ray and MR measurements of bone density and body composition, metabolic testing (intravenous glucose tolerance test), and muscle and adipose tissue biopsies. Blood will also be drawn for genetic testing and for microarray studies of leukocytes. Upon completion of the above studies, the participant will begin pioglitazone therapy. Every 4 weeks throughout the drug intervention, glycemic control, lipoprotein profile, and weight will be monitored. After 12 weeks of pioglitazone therapy, the X-ray and MR measurements of body composition, the biopsies, microarray studies for leukocytes and the metabolic tests will be repeated.
Pioglitazone: 30 mg tablet once daily for 4 weeks, then increased to 45 mg once daily for an additional 8 weeks. Total dosage period is 12 weeks.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=114 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
114 Participants
n=114 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=114 Participants
|
|
Sex: Female, Male
Female
|
64 Participants
n=114 Participants
|
|
Sex: Female, Male
Male
|
50 Participants
n=114 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=114 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=114 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=114 Participants
|
|
Race (NIH/OMB)
Black or African American
|
8 Participants
n=114 Participants
|
|
Race (NIH/OMB)
White
|
106 Participants
n=114 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=114 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=114 Participants
|
|
Insulin resistance
|
2.74 HOMA-IR index is unitless by definition
STANDARD_DEVIATION 1.82 • n=59 Participants • HOMA-IR index was calculated only on subjects who had complete data including both intravenous glucose tolerance tests
|
PRIMARY outcome
Timeframe: 12 weeksPopulation: Included subjects are those who had complete data, including HOMA-IR index at both baseline and after treatment.
Change in insulin resistance was calculated as change (end of treatment minus baseline) in HOMA-IR index (glucose (mg/dL) x insulin (μU/mL)/405)
Outcome measures
| Measure |
Pioglitazone (Actos)
n=59 Participants
The study is a one-arm design.
All participants will receive Pioglitazone: 30 mg tablet once daily for 4 weeks, then increased to 45 mg once daily for an additional 8 weeks. Total dosage period is 12 weeks.
|
|---|---|
|
Change in Insulin Resistance
|
-0.83 HOMA-IR index is unitless by definition
Standard Deviation 1.23
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Only subjects who had complete RNAseq (RNA sequencing) data and HOMA-IR were included
Number of genes determined to be correlated with change in insulin sensitivity as determined by HOMA-IR with a p-value below 0.000001
Outcome measures
| Measure |
Pioglitazone (Actos)
n=53934 Genes
The study is a one-arm design.
All participants will receive Pioglitazone: 30 mg tablet once daily for 4 weeks, then increased to 45 mg once daily for an additional 8 weeks. Total dosage period is 12 weeks.
|
|---|---|
|
Number of Genes Determined to be Correlated With Change in Insulin Sensitivity
|
7 Genes
|
Adverse Events
Pioglitazone (Actos)
Serious events: 2 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Pioglitazone (Actos)
n=114 participants at risk
Participants will have metabolism studies to consist of outpatient X-ray and MR measurements of bone density and body composition, metabolic testing (intravenous glucose tolerance test), and muscle and adipose tissue biopsies. Blood will also be drawn for genetic testing and for microarray studies of leukocytes. Upon completion of the above studies, the participant will begin pioglitazone therapy. Every 4 weeks throughout the drug intervention, glycemic control, lipoprotein profile, and weight will be monitored. After 12 weeks of pioglitazone therapy, the X-ray and MR measurements of body composition, the biopsies, microarray studies for leukocytes and the metabolic tests will be repeated.
Pioglitazone: 30 mg tablet once daily for 4 weeks, then increased to 45 mg once daily for an additional 8 weeks. Total dosage period is 12 weeks.
|
|---|---|
|
Endocrine disorders
hypoglycemia
|
0.88%
1/114 • Number of events 2 • 12 weeks (treatment phase) + 4 weeks (follow-up) = 16 weeks
|
|
Cardiac disorders
Vasovagal response
|
0.88%
1/114 • Number of events 1 • 12 weeks (treatment phase) + 4 weeks (follow-up) = 16 weeks
|
Other adverse events
| Measure |
Pioglitazone (Actos)
n=114 participants at risk
Participants will have metabolism studies to consist of outpatient X-ray and MR measurements of bone density and body composition, metabolic testing (intravenous glucose tolerance test), and muscle and adipose tissue biopsies. Blood will also be drawn for genetic testing and for microarray studies of leukocytes. Upon completion of the above studies, the participant will begin pioglitazone therapy. Every 4 weeks throughout the drug intervention, glycemic control, lipoprotein profile, and weight will be monitored. After 12 weeks of pioglitazone therapy, the X-ray and MR measurements of body composition, the biopsies, microarray studies for leukocytes and the metabolic tests will be repeated.
Pioglitazone: 30 mg tablet once daily for 4 weeks, then increased to 45 mg once daily for an additional 8 weeks. Total dosage period is 12 weeks.
|
|---|---|
|
Skin and subcutaneous tissue disorders
Hematoma at abdominal fat biopsy site
|
6.1%
7/114 • Number of events 7 • 12 weeks (treatment phase) + 4 weeks (follow-up) = 16 weeks
|
|
Endocrine disorders
Hypoglycemia during intravenous glucose tolerance test
|
7.0%
8/114 • Number of events 9 • 12 weeks (treatment phase) + 4 weeks (follow-up) = 16 weeks
|
Additional Information
Soren Snitker, MD, PhD
University of Maryland School of Medicine
Phone: 4107061511
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place