PDE5 Inhibition for Obesity-Related Cardiometabolic Dysfunction

NCT02819440 | Completed Phase 2 Results DMC

• 1 other identifier: 160208
• Study Type: interventional
• Target: 141
• Locations: 1 country
• Sites: 1

Brief Summary

Obesity and its adverse cardiometabolic consequences are major public health problems. Several features of obesity contribute to the associated cardiovascular risk and are potential targets for intervention. These include insulin resistance and beta cell dysfunction, reduced metabolic rate, and impaired aerobic capacity.The purpose of this study is to examine if the phosphodiesterase type 5A inhibitor tadalafil improves cardiometabolic health in individuals who are obese and insulin resistant.

Conditions

Healthy; Obese

Outcome Measures

Primary Outcomes (2)

• Resting Energy Expenditure After 12 Weeks of Drug Therapy (kcal/Day)

  Subjects will undergo a metabolic chamber protocol to measure resting exercise energy expenditure (kcal/min) at 12 weeks adjusted statistically for the baseline measurement.

  12 weeks

• Insulin Sensitivity After 12 Weeks of Drug Therapy

  Subjects will undergo an insulin modified fasting intravenous glucose tolerance test (FS-IVGTT) protocol at 12 weeks adjusted statistically for the baseline measurement.

  12 weeks

Secondary Outcomes (7)

• Physical Activity-induced Energy Expenditure (kcal/Day)

  12 weeks

• Dual Energy X-Ray Absorptiometry (DEXA) (g)

  12 weeks

• Quality of Life Using the Medical Outcomes Study Short-Form Health Survey (SF-36) Physical Component Score

  12 weeks

• Change in cGMP/NP Ratio After 12 Weeks of Drug Therapy

  12 weeks

• Maximal Oxygen Consumption

  12 weeks

Study Arms (2)

Tadalafil

ACTIVE COMPARATOR

Subjects will be randomized to one of two arms. 100 obese adult subjects will be randomized to the Tadalafil arm following the screening visit. Beginning at their baseline visit, they will receive an oral daily dose of Tadalafil (20mg) that they will take for 12 weeks (through their completion of the study). After randomization has occurred, the active comparator subjects will undergo the following visit protocol: baseline visit (two half-days), an interim visit (6 weeks post-baseline), and a 12-week visit (two half-days).

Drug: Tadalafil

Placebo

PLACEBO COMPARATOR

Subjects will be randomized to one of two arms. 100 obese adult subjects will be randomized to the placebo arm following the screening visit. Beginning at their baseline visit, they will receive an oral daily dose of a placebo pill (20mg) that they will take for 12 weeks (through their completion of the study). After randomization has occurred, the placebo comparator subjects will undergo the following visit protocol: baseline visit (two half-days), an interim visit (6 weeks post-baseline), and a 12-week visit (two half-days).

Drug: Placebo

Interventions

Tadalafil DRUG

Tadalafil is an FDA approved, clinically-available drug that inhibits the enzyme phosphodiesterase type 5A (PDE5). Subjects who are randomized to this arm will be provided with 20mg of Tadalafil to take every day for 12 weeks, beginning at their baseline visit.

Also known as: CIALIS

Tadalafil

Placebo DRUG

100 patients will be randomized to receive a placebo pill. Subjects in this arm will be provided with 20mg Placebo to take every day for 12 weeks, beginning at their baseline visit.

Placebo

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Adults (ages 21-50)
• Obesity (BMI ≥ 30 kg/m2)
• Prediabetes on oral glucose tolerance test.

You may not qualify if:

• Age \<21 or \> 50
• BMI \< 30 kg/m2
• 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 breastfeeding or those unwilling to avoid pregnancy during the course of the study

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37215, United States

Location

MeSH Terms

Conditions

Obesity

Interventions

Tadalafil

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Carbolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Results Point of Contact

• Title: Evan Brittain
• Organization: Vanderbilt University Medical Center

evan.brittain@vumc.org

6153224382

Study Officials

• Evan L Brittain, MD, MSCI

  Vanderbilt Cardiovascular Medicine

  PRINCIPAL INVESTIGATOR

• Thomas J Wang, MD

  Vanderbilt Cardiovascular Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 21, 2016
• First Posted: June 30, 2016
• Study Start: July 1, 2016
• Primary Completion: June 1, 2020
• Study Completion: June 1, 2020
• Last Updated: May 27, 2022
• Results First Posted: May 27, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share

Locations

US (1)