Effect of PDE5 Inhibition on Adipose Metabolism in Humans

Vanderbilt University Medical Center

Status and phase: Completed; Phase 2

Conditions: Obesity

Treatments: Drug: Placebo; Drug: Tadalafil 20 MG

Study type: Interventional

Funder types: Other

Identifiers

NCT04684589

202420

Details and patient eligibility

About

This is a randomized, double-blinded, placebo-controlled study of the effects of PDE5 inhibition with tadalafil on adipose tissue in obese individuals. Adipose metabolism will be measured using magnetic resonance imaging (MRI) scans and by aspirating a small amount of adipose to measure gene expression.

Full description

The purpose of this study is to test whether tadalafil causes subcutaneous adipose tissue to have a "beige" phenotype. Participants will be randomized to either placebo or tadalafil for 12 weeks. Investigators will study adipose metabolism using MRI scans and aspiration of subcutaneous adipose from the abdomen. In addition to MRI scans at room temperature, the investigators will use a cooling protocol to test the combined effects of tadalafil and on adipose metabolism. Investigators will also measure the effects of the drug on body composition. In addition to the study visits, participants will wear an activity tracker (Fitbit) and log their dietary intake several times using an online tool. There will be a small amount of radiation exposure. Participants will be compensated for participation in this study.

Enrollment: 89 patients

Sex: All

Ages: 19 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Adults
• Obesity (BMI ≥ 30 kg/m2)

Exclusion criteria

• Age <19 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
• 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%)
• Menopause
• Weight > 300 pounds
• Individuals with circadian rhythm disorders, shift workers, or those who travel across time zones frequently

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

89 participants in 2 patient groups, including a placebo group

Tadalafil

Active Comparator group

Description:

Subjects will be randomized to one of two arms. 50 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: screening visit, baseline visit, an interim visit (10 weeks post-baseline), and a 12-week visit.

Treatment:

Drug: Tadalafil 20 MG

Placebo

Placebo Comparator group

Description:

Subjects will be randomized to one of two arms. 50 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: screening visit, baseline, an interim visit (10 weeks post-baseline), and a 12-week visit.

Treatment:

Drug: Placebo