Obesity
Conditions
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.
Interventions
DRUGTadalafil 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.
DRUGPlacebo
Subjects in this arm will be provided with 20mg Placebo to take every day for 12 weeks, beginning at their baseline visit.
Sponsors
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double blinded
Intervention model description
Half of participants to get tadalafil and half to get placebo.
Eligibility
Sex/Gender
ALL
Age
19 Years to 50 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Thermoneutral FSF of WAT at the Level of the Umbilicus at 12 Weeks. | 12 weeks | Measured by fat signal fraction (FSF) at Week 12. FSF is the percent of MRI signal derived from lipids within a voxel. Lower FSF values indicate greater lipid consumption and correspond to brown adipose tissue (BAT), whereas higher FSF values indicate lipid storage and correspond to white adipose tissue (WAT). |
| Thermoneutral Subcutaneous Adipose Tissue Expression of UCP1 (Normalized Expression Units) at 12 Weeks. | 12 weeks | Measured by mRNA expression of subcutaneous adipose tissue obtained via biopsy at 12 weeks. Higher expression of UCP1 indicates increased thermogenic (beige/brown) adipose activity; lower expression indicates a white adipose phenotype associated with reduced energy expenditure. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATOREvan Brittain, MD, MSci
VUMC
Participant flow
Pre-assignment details
Participants underwent a screening visit to confirm eligibility criteria. Prior to randomization, eligible participants underwent baseline testing. In total, 99 participants were consented (enrolled). 10 participants failed screening. 16 participants dropped out prior to the baseline visit. In total, 73 participants were randomized.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 35 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 57 Participants |
| Sex: Female, Male Female | 26 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 37 | 0 / 36 |
| other Total, other adverse events | 28 / 37 | 8 / 36 |
| serious Total, serious adverse events | 0 / 37 | 0 / 36 |
Outcome results
None listed