Tadalafil for Obesity

Overseen By Evan Brittain, MD, MSci

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Vanderbilt University Medical Center

Must not be taking: Antihypertensives, Nitrates, PDE-5 inhibitors, others

Disqualifiers: Age, Hypertension, Cardiac history, Diabetes, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 11

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effects of tadalafil, a medication, on fat tissue metabolism in people with obesity. Researchers aim to determine if taking tadalafil daily for 12 weeks can alter fat storage and usage in the body. Participants will be randomly assigned to receive either tadalafil or a placebo (a pill with no active drug) without knowing which one they are taking. The trial seeks adults with a BMI of 30 or higher who do not have certain medical conditions or take specific medications. As a Phase 2 trial, this research focuses on measuring how well tadalafil works in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including anti-hypertensive medications, organic nitrates, PDE-5 inhibitors, and medications that strongly alter CYP3A4 activity. If you are on any of these, you would need to stop them to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that tadalafil is usually safe for people. In studies, participants taking tadalafil did not experience a higher risk of low blood pressure or heart problems, suggesting it is safe for most individuals. Tadalafil is already used for conditions like erectile dysfunction, which supports confidence in its safety. Although this trial focuses on obesity, past users of tadalafil have not encountered major issues. It is always important to consult a healthcare provider before joining any trial to understand personal risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for obesity?

Researchers are excited about Tadalafil for obesity because it offers a fresh approach compared to standard treatments like lifestyle changes, medications like Orlistat, or surgeries such as gastric bypass. Tadalafil, commonly known for treating erectile dysfunction, works by enhancing blood flow and has potential metabolic effects that might aid in weight loss. This unique mechanism differs from other obesity treatments, which often focus on appetite suppression or calorie absorption. If successful, Tadalafil could provide a novel, non-invasive option for managing obesity, especially for those who struggle with traditional methods.

What evidence suggests that tadalafil might be an effective treatment for obesity?

Research has shown that tadalafil, which participants in this trial may receive, might help reduce fat around the organs. One study found it could lower this fat and improve cholesterol levels. Another study discovered that tadalafil helped control blood sugar and improved erectile function. While some research did not find changes in insulin sensitivity, it did show positive effects on cells that help manage blood sugar. These findings suggest tadalafil might be helpful for addressing obesity-related issues. ^{1 2 5 6 7}

Who Is on the Research Team?

Evan Brittain, MD, MSci

Principal Investigator

VUMC

Are You a Good Fit for This Trial?

This trial is for adults with obesity (BMI ≥ 30 kg/m2) who are not pregnant, breastfeeding, or planning to become pregnant. Participants should not have a history of significant heart conditions, seizures, diabetes, anemia, or use medications affecting CYP3A4 enzymes. They must weigh less than 300 pounds and not be using PDE5 inhibitors or certain blood pressure medicines.

Inclusion Criteria

My BMI is 30 or higher.

I am 18 years old or older.

Exclusion Criteria

You have a history of priapism (painful and prolonged erection).

You have trouble with your sleep-wake cycle, work night shifts, or travel to different time zones frequently.

I am not pregnant, breastfeeding, and willing to prevent pregnancy during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either tadalafil or placebo for 12 weeks, with monitoring of adipose metabolism using MRI and adipose aspiration

12 weeks

Baseline visit, interim visit (10 weeks post-baseline), and 12-week visit

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Tadalafil

Trial Overview The study tests the effect of Tadalafil (a drug commonly used for erectile dysfunction), on fat metabolism in obese individuals compared to a placebo. It's randomized and double-blinded meaning neither participants nor researchers know who gets the real drug. Fat metabolism is checked by MRI scans and fat tissue sampling.

How Is the Trial Designed?

Group I: Tadalafil Active Control 1 Intervention

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: screening visit, baseline visit, an interim visit (10 weeks post-baseline), and a 12-week visit.

Group II: Placebo Placebo Group 1 Intervention

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: screening visit, baseline, an interim visit (10 weeks post-baseline), and a 12-week visit.

Tadalafil is already approved in United States, European Union for the following indications:

Approved in United States as Cialis for:

• Erectile dysfunction
• Pulmonary hypertension

Approved in European Union as Tadalafil for:

• Erectile dysfunction
• Pulmonary hypertension

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Published Research Related to This Trial

Obesity is a significant health risk, and various pharmacologic treatments are available, including recently approved agents like dexfenfluramine and sibutramine, which primarily work by inhibiting serotonin reuptake and may also affect thermogenesis.

Current research is exploring new drug targets, such as beta 3-adrenergic receptor agonists and agents that influence leptin and other biologic substances related to satiety, aiming to not only treat obesity but also prevent related conditions like diabetes and cardiovascular disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacologic approach to the treatment of obesity. Weiser, M., Frishman, WH., Michaelson, MD., et al.[2019]

Sibutramine and orlistat are the only two anti-obesity medications approved for long-term use, with sibutramine reducing food intake and orlistat inhibiting fat absorption, though orlistat can cause gastrointestinal side effects like flatulence and diarrhea.

Rimonabant, an endocannabinoid receptor antagonist approved in 2006, was suspended in 2008 due to psychiatric side effects, highlighting the need for further studies on the long-term safety and efficacy of anti-obesity medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for obesity. Li, M., Cheung, BM.[2021]

Obesity rates have more than doubled globally since 1980, leading to increased prevalence of related diseases such as diabetes and heart disease, highlighting the urgent need for effective obesity treatments.

Currently, orlistat is the only anti-obesity drug approved in Europe, while other previously used medications like sibutramine have been removed from the market due to safety concerns, emphasizing the challenges in developing safe and effective obesity therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targets for medical therapy in obesity. Baretić, M.[2012]

Tadalafil, a new oral treatment for erectile dysfunction, is highly effective with a duration of action lasting up to 36 hours, making it a convenient option for patients.

The medication has a strong safety profile, with only a few mild to moderate side effects reported, which is particularly important for patients who may have other medical conditions or take multiple medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Tadalafil for erectile dysfunction: excellent safety and tolerance]. Bai, WJ.[2015]

Tadalafil, a PDE-5 inhibitor, is effective for treating erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia, showing good tolerance in patients.

The drug is considered safe for patients with cardiovascular comorbidities and may even provide beneficial effects on cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety of tadalafil in patients with cardiovascular comorbidities]. Nikitina, IL., Gaysina, GG., Galimov, SN., et al.[2019]

A patient with obesity hypoventilation syndrome (OHS) and pulmonary hypertension (PH) showed improvement when treated with tadalafil alongside weight loss and bi-level positive airway pressure therapy.

This case suggests that tadalafil may be an effective adjunctive therapy for managing pulmonary arterial pressure in patients with OHS who do not respond adequately to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive tadalafil therapy for managing pulmonary hypertension in a patient with obesity hypoventilation syndrome. Katsuragi, S., Hara, M., Mizote, I., et al.[2020]

In a study involving 2102 men with erectile dysfunction, tadalafil significantly improved erectile function compared to placebo, with mean improvements in the International Index of Erectile Function (IIEF) scores of 6.5 and 8.6 for the 10 mg and 20 mg doses, respectively.

Tadalafil was effective for up to 36 hours after dosing and showed consistent efficacy across different severities and causes of erectile dysfunction, with common side effects including headache and back pain, indicating it is a well-tolerated treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of tadalafil: an update. Carson, CC., Rajfer, J., Eardley, I., et al.[2023]

In a study involving 18 obese men aged 30 to 50, tadalafil administration for 28 days did not significantly affect total insulin secretion or insulin sensitivity, indicating it may not be effective for improving these metabolic parameters in this population.

The study used rigorous methods, including a randomized, double-blind, placebo-controlled design, but ultimately found no beneficial effects of tadalafil on insulin-related measures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of tadalafil administration on insulin secretion and insulin sensitivity in obese men. González-Ortiz, M., Martínez-Abundis, E., Hernández-Corona, DM., et al.[2018]

In an animal model of metabolic syndrome induced by a high-fat diet, tadalafil treatment reduced visceral adipose tissue accumulation and improved hypertriglyceridemia, indicating its potential efficacy in combating metabolic syndrome.

Tadalafil promoted the differentiation of preadipocytes into metabolically healthy adipocytes, enhancing insulin sensitivity and increasing the expression of brown fat-specific markers, which suggests a mechanism for its beneficial effects on fat metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tadalafil reduces visceral adipose tissue accumulation by promoting preadipocytes differentiation towards a metabolically healthy phenotype: Studies in rabbits. Maneschi, E., Cellai, I., Aversa, A., et al.[2017]

Sibutramine and orlistat are two FDA-approved medications for long-term obesity treatment, with distinct mechanisms of action: sibutramine acts as a reuptake inhibitor of monoamines, while orlistat inhibits pancreatic lipase to reduce fat absorption.

Dexfenfluramine has been withdrawn from the market due to its association with serious heart valve issues, highlighting the importance of safety monitoring in obesity pharmacotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent progress in obesity pharmacotherapy. Ryan, DH.[2019]

In a study involving 80 participants with grade 1 obesity, a single 20 mg dose of tadalafil significantly reduced systolic and diastolic blood pressure, as well as central systolic blood pressure and arterial stiffness markers, indicating potential cardiovascular benefits.

However, tadalafil did not have an effect on flow-mediated dilation, suggesting that while it may improve certain vascular parameters, it does not enhance endothelial function in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tadalafil Improves Haemodynamics and Arterial Stiffness but Not Flow- Mediated Dilation in Grade 1 Obesity. A Single-dose, Placebo-controlled Clinical Trial. Larios-Cárdenas, M., González-Radillo, OI., Trujillo-Quirós, J., et al.[2023]

Tadalafil is generally safe and well-tolerated for chronic treatment of erectile dysfunction, even in high-risk populations, with most side effects being mild or moderate and reversible without stopping the medication.

It does not increase the risk of cardiovascular issues and can be safely used alongside antihypertensive medications and selective alpha-receptor blockers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety and tolerance of tadalafil in the treatment of erectile dysfunction]. He, XY.[2015]

Sibutramine, a serotonin/noradrenaline reuptake inhibitor, has been shown to reduce body weight by an average of 4.45 kg compared to placebo, while also improving triglycerides and HDL cholesterol, but it may cause increased heart rate and has contraindications for patients with uncontrolled hypertension or cardiovascular issues.

Orlistat, a pancreatic lipase inhibitor, results in an average weight loss of 2.89 kg and significantly decreases waist circumference and blood pressure, but primarily causes gastrointestinal side effects and should be avoided in patients with chronic malabsorption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacological therapy of obesity]. Pagotto, U., Vanuzzo, D., Vicennati, V., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9022238/

Effect of low-dose tadalafil once daily on glycemic control in ... This prospective pilot study showed that low-dose tadalafil administered once a day was effective in improving glycemic control and erectile function

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0303720716300156

Tadalafil reduces visceral adipose tissue accumulation by ... Tadalafil treatments were able to reduce visceral adipose tissue (VAT) accumulation and hypertriglyceridemia, and to induce the expression in VAT of the brown ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02554045

NCT02554045 | Daily Tadalafil on Body Fat and Lean Mass The primary purpose of the study is to investigate the effects of tadalafil taken once a day on body composition in men with sexual distress and/or erectile ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6479091/

Obesity and Erectile Dysfunction: From Bench to Clinical ... Although Ho et al [86] fail to show improvements in insulin resistance with tadalafil in obese individuals, they demonstrate a favorable effect on β-cell ...

5. link.springer.com link.springer.com/article/10.1208/s12248-024-00985-9

Erectile Dysfunction Therapy of Bariatric Patients: Tadalafil ... This mechanistic analysis suggests that tadalafil may be as effective after sleeve gastrectomy as before the procedure; meanwhile, results ...

6. academic.oup.com academic.oup.com/jsm/article/19/1/74/6961191

The Journal of Sexual Medicine | Oxford Academic This study did not demonstrate an increased risk of hypotensive or cardiovascular outcomes associated with co-possession of tadalafil and anti-hypertensive ...

7. amjmed.com amjmed.com/article/S0002-9343(24)00705-8/fulltext

Benefits of Tadalafil and Sildenafil on Mortality, ... Patients with erectile dysfunction who received tadalafil showed reduced all-cause mortality, improved cardiovascular outcomes, and lower rates ...