PDE5 Inhibition for Obesity-Related Cardiometabolic Dysfunction

• Sponsor: Vanderbilt University Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02819440
• Collaborator: (none)
• Enrollment: 141
• Location: 1
• Arms: 2
• Duration (Months): 47
• Patients Per Site Per Month: 3

Study Details

Study Description

Brief Summary

Obesity and its adverse cardiometabolic consequences are major public health problems. Several features of obesity contribute to the associated cardiovascular risk and are potential targets for intervention. These include insulin resistance and beta cell dysfunction, reduced metabolic rate, and impaired aerobic capacity.The purpose of this study is to examine if the phosphodiesterase type 5A inhibitor tadalafil improves cardiometabolic health in individuals who are obese and insulin resistant.

Condition or Disease	Intervention/Treatment	Phase
Healthy; Obese	Drug: Tadalafil; Drug: Placebo	Phase 2

Detailed Description

Obesity is a risk factor for nearly all cardiovascular (CV) disease including coronary artery disease, hypertension, and heart failure. Increased CV risk in obese individuals appears to depend largely on the degree of metabolic dysregulation and metabolic risk factors (glucose intolerance, dyslipidemia, etc.). Notably, interventions that improve insulin sensitivity and cardiorespiratory fitness can reduce CV risk in obese individuals, even in the absence of weight loss.

The cyclic guanylate monophosphate pathway (cGMP) is involved in energy homeostasis and systemic metabolism. Multiple lines of evidence suggest that increasing cGMP activity is beneficial from a metabolic standpoint. Tadalafil is a clinically-available drug that inhibits the enzyme that breaks down cGMP.

The study investigators hypothesize that chronic PDE5 inhibition in obese, insulin-resistant adults will improve cardiometabolic health.

Aim 1: To examine the effect of PDE5 inhibition on energy expenditure. Aim 2: To examine the effect of PDE5 inhibition on insulin sensitivity and secretion.

Aim 3: To examine the effect of PDE5 inhibition on cGMP tone and circulating mediators of cardiometabolic risk.

Study Design

• Study Type: Interventional
• Actual Enrollment: 141 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: PDE5 Inhibition for Obesity-Related Cardiometabolic Dysfunction
• Study Start Date: Jul 1, 2016
• Actual Primary Completion Date: Jun 1, 2020
• Actual Study Completion Date: Jun 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Tadalafil Subjects will be randomized to one of two arms. 100 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: baseline visit (two half-days), an interim visit (6 weeks post-baseline), and a 12-week visit (two half-days).	Drug: Tadalafil; 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.; Other Names: CIALIS
Placebo Comparator: Placebo Subjects will be randomized to one of two arms. 100 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: baseline visit (two half-days), an interim visit (6 weeks post-baseline), and a 12-week visit (two half-days).	Drug: Placebo; 100 patients will be randomized to receive a placebo pill. Subjects in this arm will be provided with 20mg Placebo to take every day for 12 weeks, beginning at their baseline visit.

Outcome Measures

Primary Outcome Measures

1. Resting Energy Expenditure After 12 Weeks of Drug Therapy (kcal/Day) [12 weeks]

   Subjects will undergo a metabolic chamber protocol to measure resting exercise energy expenditure (kcal/min) at 12 weeks adjusted statistically for the baseline measurement.

2. Insulin Sensitivity After 12 Weeks of Drug Therapy [12 weeks]

   Subjects will undergo an insulin modified fasting intravenous glucose tolerance test (FS-IVGTT) protocol at 12 weeks adjusted statistically for the baseline measurement.

Secondary Outcome Measures

1. Physical Activity-induced Energy Expenditure (kcal/Day) [12 weeks]

   During the metabolic chamber protocol, conducted at baseline and at 12 weeks, the cardiopulmonary exercise test protocol will be conducted. The Energy Expenditure (EE) related to physical activity will be calculated as peak EE above the resting level while performing the exercise test.

2. Dual Energy X-Ray Absorptiometry (DEXA) (g) [12 weeks]

   fat mass at 12 weeks.

3. Quality of Life Using the Medical Outcomes Study Short-Form Health Survey (SF-36) Physical Component Score [12 weeks]

   Quality of life will be assessed using the Medical Outcomes Study Short-Form Health Survey (SF-36). The SF-36 is a 36 question survey with a total score range from 0-100; higher scores indicate better quality of life.

4. Change in cGMP/NP Ratio After 12 Weeks of Drug Therapy [12 weeks]

   Subjects will undergo a fasting blood draw at baseline and 12 weeks to measure the change in ratio of plasma cyclic guanylate monophosphate pathway (cGMP) to plasma natriuretic peptides (NP) in response to the drug intervention (placebo or tadalafil).

5. Maximal Oxygen Consumption [12 weeks]

   Subjects will undergo a symptom-limited cardiopulmonary exercise test to measure peak oxygen consumption (VO2 max). Maximal oxygen consumption will be measured as 'mL/min'.

6. Sexual Function [12 weeks]

   The Female Sexual Function Index will be used to measure sexual function in women with a range from 2-36 with higher scores indicating better sexual function.

7. Maximal Exercise Energy Expenditure (kcal/Day) [12 weeks]

   Subjects will undergo a metabolic chamber protocol to measure maximal exercise energy expenditure (kcal/min) at 12 weeks adjusted statistically for the baseline measurement. Maximal Exercise Energy Expenditure will be measured as "kcal/day"

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Adults (ages 21-50)

• Obesity (BMI ≥ 30 kg/m2)

• Prediabetes on oral glucose tolerance test.

Exclusion Criteria:

• Age <21 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

• Inability to exercise on a bicycle

• Weight > 300 pounds

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37215

Sponsors and Collaborators

• Vanderbilt University Medical Center

Investigators

• Principal Investigator: Evan L Brittain, MD, MSCI, Vanderbilt Cardiovascular Medicine
• Principal Investigator: Thomas J Wang, MD, Vanderbilt Cardiovascular Medicine

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 30, 2019

More Information

Publications

None provided.

• Responsible Party: Evan Brittain, Principal Investigator, Vanderbilt University Medical Center
• ClinicalTrials.gov Identifier: NCT02819440
• Other Study ID Numbers: 160208
• First Posted: Jun 30, 2016
• Last Update Posted: May 27, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Obesity; Tadalafil

Study Results

Participant Flow

Pre-assignment Detail	141 participants passed our screening procedures and were enrolled however only 125 were randomized due to dropouts and scheduling conflicts. We allowed up to 30 days between the screening process and the baseline visit. Participants were assigned to a group after the baseline visit.

Arm/Group Title	Tadalafil	Placebo
Arm/Group Description	Subjects will be randomized to one of two arms. 100 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: baseline visit (two half-days), an interim visit (6 weeks post-baseline), and a 12-week visit (two half-days). Tadalafil: 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.	Subjects will be randomized to one of two arms. 100 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: baseline visit (two half-days), an interim visit (6 weeks post-baseline), and a 12-week visit (two half-days). Placebo: 100 patients will be randomized to receive a placebo pill. Subjects in this arm will be provided with 20mg Placebo to take every day for 12 weeks, beginning at their baseline visit.
Period Title: Overall Study
STARTED	61	64
COMPLETED	48	52
NOT COMPLETED	13	12

Baseline Characteristics

Arm/Group Title	Tadalafil	Placebo	Total
Arm/Group Description	Subjects will be randomized to one of two arms. 100 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: baseline visit (two half-days), an interim visit (6 weeks post-baseline), and a 12-week visit (two half-days). Tadalafil: 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.	Subjects will be randomized to one of two arms. 100 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: baseline visit (two half-days), an interim visit (6 weeks post-baseline), and a 12-week visit (two half-days). Placebo: 100 patients will be randomized to receive a placebo pill. Subjects in this arm will be provided with 20mg Placebo to take every day for 12 weeks, beginning at their baseline visit.	Total of all reporting groups
Overall Participants	61	64	125
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	36.5 (7.8)	36.0 (8.2)	36.2 (7.9)
Sex: Female, Male (Count of Participants)
Female	43 70.5%	44 68.8%	87 69.6%
Male	18 29.5%	20 31.3%	38 30.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 4.9%	6 9.4%	9 7.2%
Not Hispanic or Latino	58 95.1%	57 89.1%	115 92%
Unknown or Not Reported	0 0%	1 1.6%	1 0.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	2 3.1%	2 1.6%
Native Hawaiian or Other Pacific Islander	1 1.6%	0 0%	1 0.8%
Black or African American	12 19.7%	16 25%	28 22.4%
White	46 75.4%	42 65.6%	88 70.4%
More than one race	2 3.3%	4 6.3%	6 4.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	61 100%	64 100%	125 100%

Outcome Measures

1. Primary Outcome

Title	Resting Energy Expenditure After 12 Weeks of Drug Therapy (kcal/Day)
Description	Subjects will undergo a metabolic chamber protocol to measure resting exercise energy expenditure (kcal/min) at 12 weeks adjusted statistically for the baseline measurement.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tadalafil	Placebo
Arm/Group Description	Subjects will be randomized to one of two arms. 100 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: baseline visit (two half-days), an interim visit (6 weeks post-baseline), and a 12-week visit (two half-days). Tadalafil: 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.	Subjects will be randomized to one of two arms. 100 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: baseline visit (two half-days), an interim visit (6 weeks post-baseline), and a 12-week visit (two half-days). Placebo: 100 patients will be randomized to receive a placebo pill. Subjects in this arm will be provided with 20mg Placebo to take every day for 12 weeks, beginning at their baseline visit.
Measure Participants	48	52
Mean (Standard Deviation) [kcal/day]	1267 (133)	1268 (164)

2. Primary Outcome

Title	Insulin Sensitivity After 12 Weeks of Drug Therapy
Description	Subjects will undergo an insulin modified fasting intravenous glucose tolerance test (FS-IVGTT) protocol at 12 weeks adjusted statistically for the baseline measurement.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Missing data from 2 participants in the Tadalafil arm, 5 participants in the placebo arm caused by inability to obtain intravenous access, which is necessary to make measurements for this endpoint.

Arm/Group Title	Tadalafil	Placebo
Arm/Group Description	Subjects will be randomized to one of two arms. 100 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: baseline visit (two half-days), an interim visit (6 weeks post-baseline), and a 12-week visit (two half-days). Tadalafil: 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.	Subjects will be randomized to one of two arms. 100 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: baseline visit (two half-days), an interim visit (6 weeks post-baseline), and a 12-week visit (two half-days). Placebo: 100 patients will be randomized to receive a placebo pill. Subjects in this arm will be provided with 20mg Placebo to take every day for 12 weeks, beginning at their baseline visit.
Measure Participants	46	47
Median (Inter-Quartile Range) [ml/kg/min/μIU ml]	1.4	1.5

3. Secondary Outcome

Title	Physical Activity-induced Energy Expenditure (kcal/Day)
Description	During the metabolic chamber protocol, conducted at baseline and at 12 weeks, the cardiopulmonary exercise test protocol will be conducted. The Energy Expenditure (EE) related to physical activity will be calculated as peak EE above the resting level while performing the exercise test.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tadalafil	Placebo
Arm/Group Description	Subjects will be randomized to one of two arms. 100 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: baseline visit (two half-days), an interim visit (6 weeks post-baseline), and a 12-week visit (two half-days). Tadalafil: 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.	Subjects will be randomized to one of two arms. 100 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: baseline visit (two half-days), an interim visit (6 weeks post-baseline), and a 12-week visit (two half-days). Placebo: 100 patients will be randomized to receive a placebo pill. Subjects in this arm will be provided with 20mg Placebo to take every day for 12 weeks, beginning at their baseline visit.
Measure Participants	48	52
Mean (Standard Deviation) [kcal/day]	3320 (866)	3269 (714)

4. Secondary Outcome

Title	Dual Energy X-Ray Absorptiometry (DEXA) (g)
Description	fat mass at 12 weeks.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tadalafil	Placebo
Arm/Group Description	Subjects will be randomized to one of two arms. 100 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: baseline visit (two half-days), an interim visit (6 weeks post-baseline), and a 12-week visit (two half-days). Tadalafil: 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.	Subjects will be randomized to one of two arms. 100 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: baseline visit (two half-days), an interim visit (6 weeks post-baseline), and a 12-week visit (two half-days). Placebo: 100 patients will be randomized to receive a placebo pill. Subjects in this arm will be provided with 20mg Placebo to take every day for 12 weeks, beginning at their baseline visit.
Measure Participants	48	52
Mean (Standard Deviation) [grams]	47 (12)	50 (12)

5. Secondary Outcome

Title	Quality of Life Using the Medical Outcomes Study Short-Form Health Survey (SF-36) Physical Component Score
Description	Quality of life will be assessed using the Medical Outcomes Study Short-Form Health Survey (SF-36). The SF-36 is a 36 question survey with a total score range from 0-100; higher scores indicate better quality of life.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tadalafil	Placebo
Arm/Group Description	Subjects will be randomized to one of two arms. 100 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: baseline visit (two half-days), an interim visit (6 weeks post-baseline), and a 12-week visit (two half-days). Tadalafil: 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.	Subjects will be randomized to one of two arms. 100 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: baseline visit (two half-days), an interim visit (6 weeks post-baseline), and a 12-week visit (two half-days). Placebo: 100 patients will be randomized to receive a placebo pill. Subjects in this arm will be provided with 20mg Placebo to take every day for 12 weeks, beginning at their baseline visit.
Measure Participants	48	52
Mean (Standard Deviation) [score on a scale]	52.7 (5.6)	51.0 (6.9)

6. Secondary Outcome

Title	Change in cGMP/NP Ratio After 12 Weeks of Drug Therapy
Description	Subjects will undergo a fasting blood draw at baseline and 12 weeks to measure the change in ratio of plasma cyclic guanylate monophosphate pathway (cGMP) to plasma natriuretic peptides (NP) in response to the drug intervention (placebo or tadalafil).
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Due to lack of funding, the assays required to measure the participant samples were not performed and there is no data to report.

Arm/Group Title	Tadalafil	Placebo
Arm/Group Description	Subjects will be randomized to one of two arms. 100 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: baseline visit (two half-days), an interim visit (6 weeks post-baseline), and a 12-week visit (two half-days). Tadalafil: 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.	Subjects will be randomized to one of two arms. 100 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: baseline visit (two half-days), an interim visit (6 weeks post-baseline), and a 12-week visit (two half-days). Placebo: 100 patients will be randomized to receive a placebo pill. Subjects in this arm will be provided with 20mg Placebo to take every day for 12 weeks, beginning at their baseline visit.
Measure Participants	0	0

7. Secondary Outcome

Title	Maximal Oxygen Consumption
Description	Subjects will undergo a symptom-limited cardiopulmonary exercise test to measure peak oxygen consumption (VO2 max). Maximal oxygen consumption will be measured as 'mL/min'.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tadalafil	Placebo
Arm/Group Description	Subjects will be randomized to one of two arms. 100 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: baseline visit (two half-days), an interim visit (6 weeks post-baseline), and a 12-week visit (two half-days). Tadalafil: 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.	Subjects will be randomized to one of two arms. 100 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: baseline visit (two half-days), an interim visit (6 weeks post-baseline), and a 12-week visit (two half-days). Placebo: 100 patients will be randomized to receive a placebo pill. Subjects in this arm will be provided with 20mg Placebo to take every day for 12 weeks, beginning at their baseline visit.
Measure Participants	48	52
Mean (Standard Deviation) [mL/min]	883 (142)	893 (186)

8. Secondary Outcome

Title	Sexual Function
Description	The Female Sexual Function Index will be used to measure sexual function in women with a range from 2-36 with higher scores indicating better sexual function.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Test only performed in women as designed.

Arm/Group Title	Tadalafil	Placebo
Arm/Group Description	Subjects will be randomized to one of two arms. 100 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: baseline visit (two half-days), an interim visit (6 weeks post-baseline), and a 12-week visit (two half-days). Tadalafil: 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.	Subjects will be randomized to one of two arms. 100 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: baseline visit (two half-days), an interim visit (6 weeks post-baseline), and a 12-week visit (two half-days). Placebo: 100 patients will be randomized to receive a placebo pill. Subjects in this arm will be provided with 20mg Placebo to take every day for 12 weeks, beginning at their baseline visit.
Measure Participants	28	35
Mean (Standard Deviation) [score on a scale]	23.9 (6.9)	19.8 (8.9)

9. Secondary Outcome

Title	Maximal Exercise Energy Expenditure (kcal/Day)
Description	Subjects will undergo a metabolic chamber protocol to measure maximal exercise energy expenditure (kcal/min) at 12 weeks adjusted statistically for the baseline measurement. Maximal Exercise Energy Expenditure will be measured as "kcal/day"
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tadalafil	Placebo
Arm/Group Description	Subjects will be randomized to one of two arms. 100 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: baseline visit (two half-days), an interim visit (6 weeks post-baseline), and a 12-week visit (two half-days). Tadalafil: 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.	Subjects will be randomized to one of two arms. 100 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: baseline visit (two half-days), an interim visit (6 weeks post-baseline), and a 12-week visit (two half-days). Placebo: 100 patients will be randomized to receive a placebo pill. Subjects in this arm will be provided with 20mg Placebo to take every day for 12 weeks, beginning at their baseline visit.
Measure Participants	48	52
Mean (Standard Deviation) [kcal/day]	4535 (760)	4588 (976)

Adverse Events

Time Frame	Baseline to 12 weeks
Adverse Event Reporting Description	Adverse event information was collected for any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Arm/Group Title	Tadalafil		Placebo
Arm/Group Description	Subjects will be randomized to one of two arms. 100 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: baseline visit (two half-days), an interim visit (6 weeks post-baseline), and a 12-week visit (two half-days). Tadalafil: 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.		Subjects will be randomized to one of two arms. 100 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: baseline visit (two half-days), an interim visit (6 weeks post-baseline), and a 12-week visit (two half-days). Placebo: 100 patients will be randomized to receive a placebo pill. Subjects in this arm will be provided with 20mg Placebo to take every day for 12 weeks, beginning at their baseline visit.
All Cause Mortality
	Tadalafil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/61 (0%)		0/64 (0%)
Serious Adverse Events
	Tadalafil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/61 (0%)		0/64 (0%)
Other (Not Including Serious) Adverse Events
	Tadalafil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/61 (59%)		19/64 (29.7%)
Blood and lymphatic system disorders
Nosebleed	0/61 (0%)		1/64 (1.6%)
Cardiac disorders
Palpitations	4/61 (6.6%)		0/64 (0%)
Gastrointestinal disorders
Blood in stool	0/61 (0%)		1/64 (1.6%)
Heartburn	5/61 (8.2%)		0/64 (0%)
Nausea	1/61 (1.6%)		0/64 (0%)
Dysphagia	1/61 (1.6%)		0/64 (0%)
Thrush	0/61 (0%)		1/64 (1.6%)
Tonsilitis	1/61 (1.6%)		0/64 (0%)
Hepatobiliary disorders
Elevated liver enzymes	0/61 (0%)		1/64 (1.6%)
Infections and infestations
Flu	0/61 (0%)		1/64 (1.6%)
Musculoskeletal and connective tissue disorders
Back Pain	3/61 (4.9%)		1/64 (1.6%)
Extremity pain	4/61 (6.6%)		2/64 (3.1%)
Foot pain	1/61 (1.6%)		0/64 (0%)
Arm tingling	0/61 (0%)		1/64 (1.6%)
Nervous system disorders
Headache	7/61 (11.5%)		5/64 (7.8%)
Renal and urinary disorders
Fluid retention	2/61 (3.3%)		0/64 (0%)
Urinary urgency	0/61 (0%)		1/64 (1.6%)
Reproductive system and breast disorders
Vaginal spotting/breakthrough bleeding	1/61 (1.6%)		1/64 (1.6%)
Erections	1/61 (1.6%)		0/64 (0%)
Skin and subcutaneous tissue disorders
Facial cellulitis	0/61 (0%)		1/64 (1.6%)
Hair loss	0/61 (0%)		1/64 (1.6%)
Rash	5/61 (8.2%)		1/64 (1.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.