Back to resultsA Trial of Tadalafil and Glycemic Traits
Primary Purpose
Cardiovascular Disease, Insulin Resistance, Glucose Intolerance
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Tadalafil
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Cardiovascular Disease focused on measuring Tadalafil, Phosphodiesterase 5 Inhibitors, Cyclic Guanylyl Monophosphate Pathway, Pharmacologic Actions, Vasodilator Agents, Cardiovascular Agents, Obesity, Glycemic Traits, Insulin Resistance, Glucose Metabolism
Eligibility Criteria
Inclusion Criteria:
- Age > 18 years and < 50 years
- BMI > 30 kg/m2
- Fasting insulin > 10 uU/mL
Exclusion Criteria:
- Systolic blood pressure (SBP) < 100, > 150 mmHg
- Current anti-hypertensive medication use, including diuretics
- Current use of organic nitrates
- Current use of PDE-5 inhibitors (sildenafil, tadalafil, vardenafil)
- History of reaction to PDE-5 inhibitors
- Known HIV infection
- Use of medications that strongly alter CYP3A4 activity
- History of myocardial infarction, angina, uncontrolled cardiac arrhythmia, stroke, transient ischemic attack, or seizure
- Known non-arteritic ischemic optic retinopathy (NAIOR)
- History of hearing loss
- Estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 by the modified diet in renal disease (MDRD) equation
- Hepatic transaminase (AST and ALT) levels greater than three times the upper limit of normal
- Known pregnancy or those unwilling to avoid pregnancy during the course of the study
- History of priapism
- Use in excess of four alcoholic drinks daily
- History of diabetes mellitus or use of anti-diabetic medications
- Known anemia (men, Hct < 38% and women, Hct < 36%)
Sites / Locations
- Massachusetts General Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Tadalafil
Placebo
Arm Description
20 mg Tadalafil tablet taken by mouth once a day for 3 months
Placebo tablet taken by mouth once a day for 3 months
Outcomes
Primary Outcome Measures
Change in Insulin Resistance From Baseline to 3 Months, as Measured by HOMA-IR
The primary endpoint is defined as the treatment group difference in the change in insulin resistance (baseline HOMA-IR minus 3-month HOMA-IR). HOMA-IR = [fasting glucose * fasting insulin]/405
Secondary Outcome Measures
Baseline to 3-month Change in Insulin Sensitivity, as Measured by the Matsuda Index
The secondary endpoint is defined as the treatment group difference in the change in Matsuda Index (baseline minus 3-month). This index is a measure of insulin resistance derived from a frequently sampled oral glucose tolerance test, obtaining glucose and insulin levels in the fasting state, as well as 30, 60, 90, and 120 min after administration of oral glucose load. Matsuda index = 10,000/SQRT [fasting glucose*fasting insulin* (mean glucose from time 30, 60, 90, 120 min) * (mean insulin at time 30, 60, 90, and 120 min)]
Baseline to 3-month Change in Endothelial Function Measured by EndoPAT
Endothelial function was measured using the reactive hyperemia index, acquired using EndoPAT device. Peripheral arterial tonometry probes were placed on both index fingers. After a 5 min equilibration period, a blood pressure cuff was inflated to 200 mmHg and kept inflated for 5 min. The cuff was then rapidly deflated and the reactive hyperemic response pulse volume recorded, where RHI = ratio of hyperemic finger pulse volume (post-cuff inflation / pre-cuff inflation) to control finger pulse volume (post-cuff inflation / pre-cuff inflation)
Insulinogenic Index
The secondary endpoint is defined as the treatment group difference in the change in insulinogenic index (baseline minus 3-month). This index is thought to reflect insulin secretion, and is derived from fasting and 30 min-post oral glucose tolerance testing glucose and insulin values. Insulinogenic index = [fasting insulin - insulin at time 30 min] / [fasting glucose - glucose at time 30 min]
Baseline to 3 Month Change in Composite of Insulin Resistance and Sensitivity, as Measured by the Oral Disposition Index
The secondary endpoint is defined as the treatment group difference in the change in oral disposition index (baseline minus 3-month). This is thought to reflect a composite of both insulin resistance and secretion. Oral disposition index = insulinogenic index / fasting insulin
Baseline to 3-month Change in Matsuda Disposition Index
Change in disposition index from baseline to 3 months. This index is a composite measure thought to reflect insulin resistance and secretion. Matsuda disposition index = [Matsuda sensitivity index * insulinogenic index]
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01444651
Brief Title
A Trial of Tadalafil and Glycemic Traits
Official Title
Phase 3 Randomized Trial of Tadalafil and Glycemic Traits
Study Type
Interventional
2. Study Status
Record Verification Date
December 2016
Overall Recruitment Status
Completed
Study Start Date
August 2011 (undefined)
Primary Completion Date
March 2013 (Actual)
Study Completion Date
March 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Thomas J. Wang, MD
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to find out if tadalafil can help overweight and obese people metabolize blood sugar more efficiently. The investigators also want to find out if 20 mg/day of tadalafil for 3 months is safe to take without causing too many side effects. The investigators are plan to enroll 100 subjects at Massachusetts General Hospital (MGH).
Detailed Description
This study is examining changes in insulin resistance and glucose tolerance following 3 months of treatment with oral, once daily tadalafil.
The investigators primary hypotheses are that measurable decreases in insulin resistance (as measured by HOMA-IR) and increases in insulin sensitivity (as measured by the Matsuda index) will occur following 3 months of treatment with oral tadalafil 20 mg daily compared to placebo.
The investigators secondary hypotheses are that improvements in average glycemia (as measured by hemoglobin A1C), pancreatic beta cell function (as measured by the oral disposition index), and body composition (including weight, waist circumference, body mass index, and waist-hip ratio) will occur as a result of tadalafil-mediated changes in the cGMP pathway.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiovascular Disease, Insulin Resistance, Glucose Intolerance, Obesity
Keywords
Tadalafil, Phosphodiesterase 5 Inhibitors, Cyclic Guanylyl Monophosphate Pathway, Pharmacologic Actions, Vasodilator Agents, Cardiovascular Agents, Obesity, Glycemic Traits, Insulin Resistance, Glucose Metabolism
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
73 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tadalafil
Arm Type
Active Comparator
Arm Description
20 mg Tadalafil tablet taken by mouth once a day for 3 months
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo tablet taken by mouth once a day for 3 months
Intervention Type
Drug
Intervention Name(s)
Tadalafil
Other Intervention Name(s)
Adcirca, Cialis
Intervention Description
20 mg Tadalafil taken once a day for 3 months
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Sugar pill
Intervention Description
Placebo tablet taken by mouth once a day for 3 months
Primary Outcome Measure Information:
Title
Change in Insulin Resistance From Baseline to 3 Months, as Measured by HOMA-IR
Description
The primary endpoint is defined as the treatment group difference in the change in insulin resistance (baseline HOMA-IR minus 3-month HOMA-IR). HOMA-IR = [fasting glucose * fasting insulin]/405
Time Frame
Baseline and 3 months
Secondary Outcome Measure Information:
Title
Baseline to 3-month Change in Insulin Sensitivity, as Measured by the Matsuda Index
Description
The secondary endpoint is defined as the treatment group difference in the change in Matsuda Index (baseline minus 3-month). This index is a measure of insulin resistance derived from a frequently sampled oral glucose tolerance test, obtaining glucose and insulin levels in the fasting state, as well as 30, 60, 90, and 120 min after administration of oral glucose load. Matsuda index = 10,000/SQRT [fasting glucose*fasting insulin* (mean glucose from time 30, 60, 90, 120 min) * (mean insulin at time 30, 60, 90, and 120 min)]
Time Frame
Baseline and 3 months
Title
Baseline to 3-month Change in Endothelial Function Measured by EndoPAT
Description
Endothelial function was measured using the reactive hyperemia index, acquired using EndoPAT device. Peripheral arterial tonometry probes were placed on both index fingers. After a 5 min equilibration period, a blood pressure cuff was inflated to 200 mmHg and kept inflated for 5 min. The cuff was then rapidly deflated and the reactive hyperemic response pulse volume recorded, where RHI = ratio of hyperemic finger pulse volume (post-cuff inflation / pre-cuff inflation) to control finger pulse volume (post-cuff inflation / pre-cuff inflation)
Time Frame
Baseline and 3 months
Title
Insulinogenic Index
Description
The secondary endpoint is defined as the treatment group difference in the change in insulinogenic index (baseline minus 3-month). This index is thought to reflect insulin secretion, and is derived from fasting and 30 min-post oral glucose tolerance testing glucose and insulin values. Insulinogenic index = [fasting insulin - insulin at time 30 min] / [fasting glucose - glucose at time 30 min]
Time Frame
Baseline and 3 months
Title
Baseline to 3 Month Change in Composite of Insulin Resistance and Sensitivity, as Measured by the Oral Disposition Index
Description
The secondary endpoint is defined as the treatment group difference in the change in oral disposition index (baseline minus 3-month). This is thought to reflect a composite of both insulin resistance and secretion. Oral disposition index = insulinogenic index / fasting insulin
Time Frame
Baseline and 3 months
Title
Baseline to 3-month Change in Matsuda Disposition Index
Description
Change in disposition index from baseline to 3 months. This index is a composite measure thought to reflect insulin resistance and secretion. Matsuda disposition index = [Matsuda sensitivity index * insulinogenic index]
Time Frame
Baseline and 3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Age > 18 years and < 50 years
BMI > 30 kg/m2
Fasting insulin > 10 uU/mL
Exclusion Criteria:
Systolic blood pressure (SBP) < 100, > 150 mmHg
Current anti-hypertensive medication use, including diuretics
Current use of organic nitrates
Current use of PDE-5 inhibitors (sildenafil, tadalafil, vardenafil)
History of reaction to PDE-5 inhibitors
Known HIV infection
Use of medications that strongly alter CYP3A4 activity
History of myocardial infarction, angina, uncontrolled cardiac arrhythmia, stroke, transient ischemic attack, or seizure
Known non-arteritic ischemic optic retinopathy (NAIOR)
History of hearing loss
Estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 by the modified diet in renal disease (MDRD) equation
Hepatic transaminase (AST and ALT) levels greater than three times the upper limit of normal
Known pregnancy or those unwilling to avoid pregnancy during the course of the study
History of priapism
Use in excess of four alcoholic drinks daily
History of diabetes mellitus or use of anti-diabetic medications
Known anemia (men, Hct < 38% and women, Hct < 36%)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas J Wang, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
25213566
Citation
Ho JE, Arora P, Walford GA, Ghorbani A, Guanaga DP, Dhakal BP, Nathan DI, Buys ES, Florez JC, Newton-Cheh C, Lewis GD, Wang TJ. Effect of phosphodiesterase inhibition on insulin resistance in obese individuals. J Am Heart Assoc. 2014 Sep 11;3(5):e001001. doi: 10.1161/JAHA.114.001001.
Results Reference
derived
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A Trial of Tadalafil and Glycemic Traits
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