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A Trial of Tadalafil and Glycemic Traits

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Thomas J. Wang, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01444651
First received: August 3, 2011
Last updated: December 4, 2016
Last verified: December 2016
  Purpose
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).

Condition Intervention Phase
Cardiovascular Disease Insulin Resistance Glucose Intolerance Obesity Drug: Tadalafil Drug: Placebo Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Phase 3 Randomized Trial of Tadalafil and Glycemic Traits

Resource links provided by NLM:


Further study details as provided by Thomas J. Wang, MD, Massachusetts General Hospital:

Primary Outcome Measures:
  • Change in Insulin Resistance From Baseline to 3 Months, as Measured by HOMA-IR [ Time Frame: Baseline and 3 months ]
    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 [ Time Frame: Baseline and 3 months ]
    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 [ Time Frame: Baseline and 3 months ]
    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 [ Time Frame: Baseline and 3 months ]
    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 [ Time Frame: Baseline and 3 months ]
    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 [ Time Frame: Baseline and 3 months ]
    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]


Enrollment: 73
Study Start Date: August 2011
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Tadalafil
20 mg Tadalafil tablet taken by mouth once a day for 3 months
Drug: Tadalafil
20 mg Tadalafil taken once a day for 3 months
Other Name: Adcirca, Cialis
Placebo Comparator: Placebo
Placebo tablet taken by mouth once a day for 3 months
Drug: Placebo
Placebo tablet taken by mouth once a day for 3 months
Other Name: Sugar pill

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

Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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%)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01444651

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States
Sponsors and Collaborators
Thomas J. Wang, MD
Investigators
Principal Investigator: Thomas J Wang, MD Massachusetts General Hospital
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Thomas J. Wang, MD, Associate Professor of Medicine, Harvard Medical School, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01444651     History of Changes
Other Study ID Numbers: 2010P-001519
Study First Received: August 3, 2011
Results First Received: July 11, 2016
Last Updated: December 4, 2016

Keywords provided by Thomas J. Wang, MD, Massachusetts General Hospital:
Tadalafil
Phosphodiesterase 5 Inhibitors
Cyclic Guanylyl Monophosphate Pathway
Pharmacologic Actions
Vasodilator Agents
Cardiovascular Agents
Obesity
Glycemic Traits
Insulin Resistance
Glucose Metabolism

Additional relevant MeSH terms:
Cardiovascular Diseases
Insulin Resistance
Glucose Intolerance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Hyperglycemia
Tadalafil
Phosphodiesterase 5 Inhibitors
Vasodilator Agents
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents

ClinicalTrials.gov processed this record on June 27, 2017