Effect of PDE5 Inhibition on Adipose Metabolism in Humans

Obesity Clinical Trial

Official title:

Effect of PDE5 Inhibition on Adipose Metabolism in Humans

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04684589
• Other study ID #: 202420
• Status: Recruiting
• Phase: Phase 2
• Start date: March 16, 2021
• Est. completion date: December 2025

Study information

• Verified date: April 2024
• Source: Vanderbilt University Medical Center
• Contact: Rashundra Oggs, NP
• Phone: 615-875-7975
• Email: rashundra.n.oggs[@]vumc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 19 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Obesity

Intervention

Drug:
• Tadalafil 20 MG
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.
• Placebo
Subjects in this arm will be provided with 20mg Placebo to take every day for 12 weeks, beginning at their baseline visit.

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	BAT perfusion under thermoneutral and cold conditions	MRI measurement of blood flow	Baseline to 12 weeks
Other	Change in BNP concentration during cold exposure	Blood measurement of hormone	Baseline to 12 weeks
Other	Change in free fatty acid level during cold exposure	Blood measurement of fat	Baseline to 12 weeks
Other	Change in whole body subcutaneous and visceral fat mass	Measurement of fat mass will be examined using dual x-ray absorptiometry to assess for changes in fat mass.	Baseline to 12 weeks
Other	Resting energy expenditure	Measurement of energy expended	Baseline to 12 Weeks
Other	Homeostatic Index of Insulin Resistance	Blood measurement of insulin resistance	Baseline to 12 Weeks
Primary	Thermoneutral FSF of WAT at the level of the umbilicus at 12 Weeks.	MRI measurement of lipid content	12 weeks
Primary	Subcutaneous adipose tissue expression of UCP1 (normalized expression units)	Measurement of gene expression in adipose sample	12 weeks
Secondary	Thermoneutral fat signal fraction of brown adipose tissue	MRI measurement of lipid content	Baseline to 12 weeks
Secondary	Cold-exposed fat signal fraction of white adipose tissue and grown adipose tissue	MRI measurement of lipid content	Baseline to 12 weeks
Secondary	Subcutaneous adipose tissue gene expression of mitochondrial genes (normalized expression units)	Measurement of gene expression in adipose sample	Baseline to 12 weeks
Secondary	Subcutaneous adipose tissue natriuretic peptide receptor expression	Measurement of gene expression in adipose sample	Baseline to 12 weeks