Clinical trial NCT01444651: A Trial of Tadalafil and Glycemic Traits
Official title: Phase 3 Randomized Trial of Tadalafil and Glycemic Traits
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: 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
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2011-10-03
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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%)

Primary outcomes:
measure: Change in Insulin Resistance From Baseline to 3 Months, as Measured by HOMA-IR
timeFrame: Baseline and 3 months
Secondary outcomes:
measure: Baseline to 3-month Change in Insulin Sensitivity, as Measured by the Matsuda Index
timeFrame: Baseline and 3 months
measure: Baseline to 3-month Change in Endothelial Function Measured by EndoPAT
timeFrame: Baseline and 3 months
measure: Insulinogenic Index
timeFrame: Baseline and 3 months
measure: Baseline to 3 Month Change in Composite of Insulin Resistance and Sensitivity, as Measured by the Oral Disposition Index
timeFrame: Baseline and 3 months
measure: Baseline to 3-month Change in Matsuda Disposition Index
timeFrame: Baseline and 3 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Thomas J Wang, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.