Effect of PDE5 Inhibition on Adipose Metabolism in Humans

NCT04684589 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: 202420
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Obesity

Outcome Measures

Primary Outcomes (2)

• Thermoneutral FSF of WAT at the level of the umbilicus at 12 Weeks.

  MRI measurement of lipid content

  12 weeks

• Subcutaneous adipose tissue expression of UCP1 (normalized expression units)

  Measurement of gene expression in adipose sample

  12 weeks

Secondary Outcomes (4)

• Thermoneutral fat signal fraction of brown adipose tissue

  Baseline to 12 weeks

• Cold-exposed fat signal fraction of white adipose tissue and grown adipose tissue

  Baseline to 12 weeks

• Subcutaneous adipose tissue gene expression of mitochondrial genes (normalized expression units)

  Baseline to 12 weeks

• Subcutaneous adipose tissue natriuretic peptide receptor expression

  Baseline to 12 weeks

Other Outcomes (6)

• BAT perfusion under thermoneutral and cold conditions

  Baseline to 12 weeks

• Change in BNP concentration during cold exposure

  Baseline to 12 weeks

• Change in free fatty acid level during cold exposure

  Baseline to 12 weeks

Study Arms (2)

Tadalafil

ACTIVE COMPARATOR

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.

Drug: Tadalafil 20 MG

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Tadalafil 20 MG 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

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

You may qualify if:

• Adults
• Obesity (BMI ≥ 30 kg/m2)

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37203, 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

Study Officials

• Evan Brittain, MD, MSci

  VUMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Model Details: Half of participants to get tadalafil and half to get placebo.

Study Record Dates

• First Submitted: December 16, 2020
• First Posted: December 24, 2020
• Study Start: March 16, 2021
• Primary Completion: June 20, 2025
• Study Completion: June 24, 2025
• Last Updated: August 29, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)