Cardiovascular DiseasePhase 3NCT01444651
A Trial of Tadalafil and Glycemic Traits
A Phase 3 study testing Tadalafil in people with Cardiovascular Disease and Insulin Resistance, run by Thomas J. Wang, MD at 1 site in United States.
Trial summary
The purpose of this study is to find out if tadalafil can help overweight and obese people metabolize blood sugar more efficiently. The investigators also want to find out if 20 mg/day of tadalafil for 3 months is safe to take without causing too many side effects. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Cardiovascular Disease, Insulin Resistance, Glucose Intolerance
- What is being tested?
- Tadalafil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 73 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2011to Mar 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age > 18 years and < 50 years
- BMI > 30 kg/m2
- Fasting insulin > 10 uU/mL
Who cannot join
- 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
Show all 17Show fewer
- 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 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%)
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts
About this study
Official title: Phase 3 Randomized Trial of Tadalafil and Glycemic Traits
The purpose of this study is to find out if tadalafil can help overweight and obese people metabolize blood sugar more efficiently. The investigators also want to find out if 20 mg/day of tadalafil for 3 months is safe to take without causing too many side effects. The investigators are plan to enroll 100 subjects at Massachusetts General Hospital (MGH).
Read the detailed description
This study is examining changes in insulin resistance and glucose tolerance following 3 months of treatment with oral, once daily tadalafil.
The investigators primary hypotheses are that measurable decreases in insulin resistance (as measured by HOMA-IR) and increases in insulin sensitivity (as measured by the Matsuda index) will occur following 3 months of treatment with oral tadalafil 20 mg daily compared to placebo.
The investigators secondary hypotheses are that improvements in average glycemia (as measured by hemoglobin A1C), pancreatic beta cell function (as measured by the oral disposition index), and body composition (including weight, waist circumference, body mass index, and waist-hip ratio) will occur as a result of tadalafil-mediated changes in the cGMP pathway.
- Being tested
- Tadalafil, Placebo
- Keywords
- Tadalafil, Phosphodiesterase 5 Inhibitors, Cyclic Guanylyl Monophosphate Pathway, Pharmacologic Actions, Vasodilator Agents, Cardiovascular Agents, Obesity, Glycemic Traits, Insulin Resistance, Glucose Metabolism
- Medical subject headings
- Cardiovascular Diseases, Insulin Resistance, Glucose Intolerance, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TadalafilDrug
Also called Adcirca, Cialis
20 mg Tadalafil taken once a day for 3 months
PlaceboDrug
Also called Sugar pill
Placebo tablet taken by mouth once a day for 3 months
| Study group | Role | What they receive |
|---|---|---|
| Tadalafil | Active comparator | 20 mg Tadalafil tablet taken by mouth once a day for 3 months Receives: Drug: Tadalafil |
| Placebo | Placebo comparator | Placebo tablet taken by mouth once a day for 3 months Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Insulin Resistance From Baseline to 3 Months, as Measured by HOMA-IR
The primary endpoint is defined as the treatment group difference in the change in insulin resistance (baseline HOMA-IR minus 3-month HOMA-IR). HOMA-IR = [fasting glucose * fasting insulin]/405
Measured: Baseline and 3 months
Secondary outcomes (5)
Baseline to 3-month Change in Insulin Sensitivity, as Measured by the Matsuda Index
The secondary endpoint is defined as the treatment group difference in the change in Matsuda Index (baseline minus 3-month). This index is a measure of insulin resistance derived from a frequently sampled oral glucose tolerance test, obtaining glucose and insulin levels in the fasting state, as well as 30, 60, 90, and 120 min after administration of oral glucose load. Matsuda index = 10,000/SQRT [fasting glucose*fasting insulin* (mean glucose from time 30, 60, 90, 120 min) * (mean insulin at time 30, 60, 90, and 120 min)]
Measured: Baseline and 3 months
Baseline to 3-month Change in Endothelial Function Measured by EndoPAT
Endothelial function was measured using the reactive hyperemia index, acquired using EndoPAT device. Peripheral arterial tonometry probes were placed on both index fingers. After a 5 min equilibration period, a blood pressure cuff was inflated to 200 mmHg and kept inflated for 5 min. The cuff was then rapidly deflated and the reactive hyperemic response pulse volume recorded, where RHI = ratio of hyperemic finger pulse volume (post-cuff inflation / pre-cuff inflation) to control finger pulse volume (post-cuff inflation / pre-cuff inflation)
Measured: Baseline and 3 months
Insulinogenic Index
The secondary endpoint is defined as the treatment group difference in the change in insulinogenic index (baseline minus 3-month). This index is thought to reflect insulin secretion, and is derived from fasting and 30 min-post oral glucose tolerance testing glucose and insulin values. Insulinogenic index = [fasting insulin - insulin at time 30 min] / [fasting glucose - glucose at time 30 min]
Measured: Baseline and 3 months
Baseline to 3 Month Change in Composite of Insulin Resistance and Sensitivity, as Measured by the Oral Disposition Index
The secondary endpoint is defined as the treatment group difference in the change in oral disposition index (baseline minus 3-month). This is thought to reflect a composite of both insulin resistance and secretion. Oral disposition index = insulinogenic index / fasting insulin
Measured: Baseline and 3 months
Baseline to 3-month Change in Matsuda Disposition Index
Change in disposition index from baseline to 3 months. This index is a composite measure thought to reflect insulin resistance and secretion. Matsuda disposition index = [Matsuda sensitivity index * insulinogenic index]
Measured: Baseline and 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2011 (estimated)
- Study startAug 2011
- Primary completionMar 2013
- Study completionMar 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 73 participants (actual)
Sponsor and investigators
- Lead sponsor
- Thomas J. Wang, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Thomas J. Wang, MD, Massachusetts General Hospital
- Investigators
- Thomas J Wang, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01444651
- Sponsor's protocol ID
- 2010P-001519
- Status last verified
- Dec 2016
- First submitted
- 3 Aug 2011
- Last updated
- 30 Jan 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Ho JE, Arora P, Walford GA, Ghorbani A, Guanaga DP, Dhakal BP, Nathan DI, Buys ES, Florez JC, Newton-Cheh C, Lewis GD, Wang TJ. Effect of phosphodiesterase inhibition on insulin resistance in obese individuals. J Am Heart Assoc. 2014 Sep 11;3(5):e001001. doi: 10.1161/JAHA.114.001001.
PubMed 25213566
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 3 Randomized Trial of Tadalafil and Glycemic Traits
- ClinicalTrials.gov ID
- NCT01444651
- Acronym / sponsor ID
- 2010P-001519
- Keywords
- Tadalafil, Phosphodiesterase 5 Inhibitors, Cyclic Guanylyl Monophosphate Pathway, Pharmacologic Actions, Vasodilator Agents, Cardiovascular Agents, Obesity, Glycemic Traits
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 73 participants (actual)
- Lead sponsor
- Thomas J. Wang, MDUniversity, hospital or other
- Study start
- Aug 2011
- Primary completion
- Mar 2013 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 3 Oct 2011 (estimated)
- Results
- Posted 30 Jan 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to find out if tadalafil can help overweight and obese people metabolize blood sugar more efficiently. The investigators also want to find out if 20 mg/day of tadalafil for 3 months is safe to take without causing too many side effects. The investigators are plan to enroll 100 subjects at Massachusetts General Hospital (MGH).
Detailed description
This study is examining changes in insulin resistance and glucose tolerance following 3 months of treatment with oral, once daily tadalafil.
The investigators primary hypotheses are that measurable decreases in insulin resistance (as measured by HOMA-IR) and increases in insulin sensitivity (as measured by the Matsuda index) will occur following 3 months of treatment with oral tadalafil 20 mg daily compared to placebo.
The investigators secondary hypotheses are that improvements in average glycemia (as measured by hemoglobin A1C), pancreatic beta cell function (as measured by the oral disposition index), and body composition (including weight, waist circumference, body mass index, and waist-hip ratio) will occur as a result of tadalafil-mediated changes in the cGMP pathway.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tadalafil | Active comparator | Drug: Tadalafil20 mg Tadalafil tablet taken by mouth once a day for 3 months |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo tablet taken by mouth once a day for 3 months |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Age > 18 years and < 50 years
- BMI > 30 kg/m2
- Fasting insulin > 10 uU/mL
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TadalafilAlso: Adcirca, Cialis20 mg Tadalafil taken once a day for 3 months | Drug | Tadalafil |
| PlaceboAlso: Sugar pillPlacebo tablet taken by mouth once a day for 3 months | Drug | Placebo |
Primary outcome
Change in Insulin Resistance From Baseline to 3 Months, as Measured by HOMA-IR
Time frame: Baseline and 3 months
The primary endpoint is defined as the treatment group difference in the change in insulin resistance (baseline HOMA-IR minus 3-month HOMA-IR). HOMA-IR = [fasting glucose * fasting insulin]/405
5 secondary outcomes
Baseline to 3-month Change in Insulin Sensitivity, as Measured by the Matsuda Index
Time frame: Baseline and 3 months
Baseline to 3-month Change in Endothelial Function Measured by EndoPAT
Time frame: Baseline and 3 months
Insulinogenic Index
Time frame: Baseline and 3 months
Baseline to 3 Month Change in Composite of Insulin Resistance and Sensitivity, as Measured by the Oral Disposition Index
Time frame: Baseline and 3 months
Baseline to 3-month Change in Matsuda Disposition Index
Time frame: Baseline and 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25213566Ho JE, Arora P, Walford GA, Ghorbani A, Guanaga DP, Dhakal BP, Nathan DI, Buys ES, Florez JC, Newton-Cheh C, Lewis GD, Wang TJ. Effect of phosphodiesterase inhibition on insulin resistance in obese individuals. J Am Heart Assoc. 2014 Sep 11;3(5):e001001. doi: 10.1161/JAHA.114.001001.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas J Wang, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tadalafil in people with Cardiovascular Disease and Insulin Resistance, run by Thomas J. Wang, MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Insulin Resistance From Baseline to 3 Months, as Measured by HOMA-IR (time frame: Baseline and 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01444651, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2017; AzTrials last refreshed its copy on 7 Nov 2026.