Trial Outcomes & Findings for Effect of PDE5 Inhibition on Adipose Metabolism in Humans (NCT NCT04684589)

Last Updated: 2026-07-30

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

99 participants

Primary outcome timeframe

12 weeks

Results posted on

2026-07-30

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Tadalafil 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 the baseline visit followed by randomization, the active comparator subjects will undergo the following visit protocol: an interim visit (10 weeks post-baseline), and a 12-week visit.	Placebo 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 the baseline visit followed by randomization, the placebo comparator subjects will undergo the following visit protocol: an interim visit (10 weeks post-baseline), and a 12-week visit.
Overall Study STARTED	37	36
Overall Study COMPLETED	26	30
Overall Study NOT COMPLETED	11	6

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effect of PDE5 Inhibition on Adipose Metabolism in Humans

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tadalafil n=37 Participants 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: an interim visit (10 weeks post-baseline), and a 12-week visit.	Placebo n=36 Participants 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: an interim visit (10 weeks post-baseline), and a 12-week visit.	Total n=73 Participants Total of all reporting groups
Age, Continuous	34 Years n=20 Participants	36 Years n=20 Participants	35 Years n=40 Participants
Sex: Female, Male Female	26 Participants n=20 Participants	26 Participants n=20 Participants	52 Participants n=40 Participants
Sex: Female, Male Male	11 Participants n=20 Participants	10 Participants n=20 Participants	21 Participants n=40 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=20 Participants	1 Participants n=20 Participants	1 Participants n=40 Participants
Race (NIH/OMB) Asian	2 Participants n=20 Participants	0 Participants n=20 Participants	2 Participants n=40 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=20 Participants	0 Participants n=20 Participants	1 Participants n=40 Participants
Race (NIH/OMB) Black or African American	6 Participants n=20 Participants	5 Participants n=20 Participants	11 Participants n=40 Participants
Race (NIH/OMB) White	27 Participants n=20 Participants	30 Participants n=20 Participants	57 Participants n=40 Participants
Race (NIH/OMB) More than one race	0 Participants n=20 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=20 Participants	0 Participants n=20 Participants	1 Participants n=40 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=20 Participants	1 Participants n=20 Participants	5 Participants n=40 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	33 Participants n=20 Participants	35 Participants n=20 Participants	68 Participants n=40 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=20 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants

PRIMARY outcome

Timeframe: 12 weeks

Outcome measures

Outcome measures
Measure	Tadalafil n=12 Participants 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: an interim visit (10 weeks post-baseline), and a 12-week visit.	Placebo n=10 Participants 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: an interim visit (10 weeks post-baseline), and a 12-week visit.
Thermoneutral FSF of WAT at the Level of the Umbilicus at 12 Weeks.	94.58 % of voxel Interval 94.49 to 95.32	94.29 % of voxel Interval 93.45 to 95.16

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Tadalafil n=25 Participants 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: an interim visit (10 weeks post-baseline), and a 12-week visit.	Placebo n=30 Participants 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: an interim visit (10 weeks post-baseline), and a 12-week visit.
Thermoneutral Subcutaneous Adipose Tissue Expression of UCP1 (Normalized Expression Units) at 12 Weeks.	0.31 normalized expression units Interval 0.21 to 0.37	0.33 normalized expression units Interval 0.28 to 0.47

Adverse Events

Tadalafil

Serious events: 0 serious events

Other events: 28 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Tadalafil n=37 participants at risk 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 a baseline visit followed by randomization, the active comparator subjects will undergo the following visit protocol: an interim visit (10 weeks post-baseline), and a 12-week visit.	Placebo n=36 participants at risk 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 a baseline visit followed by randomization, the placebo comparator subjects will undergo the following visit protocol: an interim visit (10 weeks post-baseline), and a 12-week visit.
Musculoskeletal and connective tissue disorders Muscle Pain/Cramps	8.1% 3/37 • from enrollment until end of follow-up, up to 12 weeks We report all serious adverse events and all adverse events that occurred in \>5% of participants.	2.8% 1/36 • from enrollment until end of follow-up, up to 12 weeks We report all serious adverse events and all adverse events that occurred in \>5% of participants.
Gastrointestinal disorders Heartburn	32.4% 12/37 • from enrollment until end of follow-up, up to 12 weeks We report all serious adverse events and all adverse events that occurred in \>5% of participants.	11.1% 4/36 • from enrollment until end of follow-up, up to 12 weeks We report all serious adverse events and all adverse events that occurred in \>5% of participants.
Nervous system disorders Headache	32.4% 12/37 • from enrollment until end of follow-up, up to 12 weeks We report all serious adverse events and all adverse events that occurred in \>5% of participants.	8.3% 3/36 • from enrollment until end of follow-up, up to 12 weeks We report all serious adverse events and all adverse events that occurred in \>5% of participants.
Musculoskeletal and connective tissue disorders low back pain	8.1% 3/37 • from enrollment until end of follow-up, up to 12 weeks We report all serious adverse events and all adverse events that occurred in \>5% of participants.	0.00% 0/36 • from enrollment until end of follow-up, up to 12 weeks We report all serious adverse events and all adverse events that occurred in \>5% of participants.

Additional Information

Thomas E Strayer, PhD

Vanderbilt University Medical Center

Phone: 615-936-0156

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place