Clinical trial NCT04684589: Effect of PDE5 Inhibition on Adipose Metabolism in Humans
Official title: Effect of PDE5 Inhibition on Adipose Metabolism in Humans
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Obesity
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
First posted: 2020-12-24
Enrollment: 100
Sex: ALL
Minimum age (years): 19
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Half of participants to get tadalafil and half to get placebo.
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Thermoneutral FSF of WAT at the level of the umbilicus at 12 Weeks.
timeFrame: 12 weeks
measure: Subcutaneous adipose tissue expression of UCP1 (normalized expression units)
timeFrame: 12 weeks
Secondary outcomes:
measure: Thermoneutral fat signal fraction of brown adipose tissue
timeFrame: Baseline to 12 weeks
measure: Cold-exposed fat signal fraction of white adipose tissue and grown adipose tissue
timeFrame: Baseline to 12 weeks
measure: Subcutaneous adipose tissue gene expression of mitochondrial genes (normalized expression units)
timeFrame: Baseline to 12 weeks
measure: Subcutaneous adipose tissue natriuretic peptide receptor expression
timeFrame: Baseline to 12 weeks
Other outcomes:
measure: BAT perfusion under thermoneutral and cold conditions
timeFrame: Baseline to 12 weeks
measure: Change in BNP concentration during cold exposure
timeFrame: Baseline to 12 weeks
measure: Change in free fatty acid level during cold exposure
timeFrame: Baseline to 12 weeks
measure: Change in whole body subcutaneous and visceral fat mass
timeFrame: Baseline to 12 weeks
measure: Resting energy expenditure
timeFrame: Baseline to 12 Weeks
measure: Homeostatic Index of Insulin Resistance
timeFrame: Baseline to 12 Weeks
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: VUMC
name: Evan Brittain, MD, MSci
role: PRINCIPAL_INVESTIGATOR
References: