Impaired Glucose TolerancePhase 4NCT01409993
Renin-Angiotensin and Fibrinolysis in Humans: Effect of Long-Term PDE5 Inhibition on Glucose Homeostasis
A Phase 4 study testing Sildenafil, Hyperglycemic clamp and Euglycemic clamp in people with Impaired Glucose Tolerance, run by Vanderbilt University at 1 site in United States.
Trial summary
The purpose of this study is to determine the effect of chronic PDE5 inhibitor therapy on glucose metabolism in persons with prediabetes. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Impaired Glucose Tolerance
- What is being tested?
- Sildenafil, Hyperglycemic clamp and Euglycemic clamp
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 78 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2011to Nov 2016
- Phase
- Phase 4
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 18 years and BMI > 25 kg/M2 (> 23 kg/M2 among Asian Americans) Elevated fasting plasma glucose (100-125 mg/dL) IGT (2 hour plasma glucose 140-199 mg/dL) OR metabolic syndrome and/or hemoglobin A1c 5.7-6.4%
Who cannot join
- Diabetes type 1 or type 2, as defined by a fasting glucose of 126 mg/dL or greater, a two hour plasma glucose of 200 mg/dL or greater, or the use of anti-diabetic medication.
- The use of nitrates or any disease that might require the use of nitrates.
- The use of any potent CYP3A4 inhibitor.
- subjects who have participated in a weight-reduction program during the last 6 month or whose weight has increased or decreased more than 2 kg over the preceding 6 months.
- Pregnancy. Women of child-bearing potential will be required to have undergone tubal ligation or to be using barrier methods of birth control.
- Breast-feeding.
Show all 25Show fewer
- Cardiovascular disease such as myocardial infarction within 6 months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure (LV hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis or hypertrophic cardiomyopathy.
- Treatment with anticoagulants.
- Treatment with metformin.
- History of serious neurologic disease such as cerebral hemorrhage, stroke, or transient ischemic attack.
- History or presence of immunological or hematological disorders.
- Diagnosis of asthma.
- Clinically significant gastrointestinal impairment that could interfere with drug absorption.
- Impaired hepatic function (aspartate amino transaminase [AST] and/or alanine amino.
- transaminase [ALT] >1.5 x upper limit of normal range)
- Impaired renal function (serum creatinine >1.5 mg/dl).
- Hematocrit <35%.
- Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult.
- Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days in
- 1 month).
- Treatment with lithium salts.
- History of alcohol or drug abuse.
- Treatment with any investigational drug in the 1 month preceding the study.
- Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study.
- Inability to comply with the protocol, e.g. uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to determine the effect of chronic PDE5 inhibitor therapy on glucose metabolism in persons with prediabetes.
- Conditions
- Impaired Glucose Tolerance
- Being tested
- Sildenafil, Placebo, Hyperglycemic clamp, Euglycemic clamp
- Keywords
- BMI greater than 25, Elevated fasting blood sugar (100-125mg/dL)
- Medical subject headings
- Glucose Intolerance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SildenafilDrug
Sildenafil 25 mg by mouth three times a day for three months
PlaceboDrug
Matching placebo three times a day for three months
Hyperglycemic clampDiagnostic test
Subjects with prediabetes will have a baseline hyperglycemic clamp (Aim 1) and then receive sildenafil or placebo for 3 months. Another hyperglycemic clamp will be performed followed by another 3 months off drug and an oral glucose tolerance test.
Euglycemic clampDiagnostic test
Subjects with prediabetes will have a baseline euglycemic clamp (Aim 2) and then receive sildenafil or placebo for 3 months. Another euglycemic clamp will be performed followed by another 3 months off drug and an oral glucose tolerance test.
| Study group | Role | What they receive |
|---|---|---|
| sildenafil Aim 1 | Experimental | sildenafil 25 mg p.o. tid Receives: Drug: Sildenafil; Diagnostic Test: Hyperglycemic clamp |
| placebo Aim 1 | Placebo comparator | matching placebo p.o. tid Receives: Drug: Placebo; Diagnostic Test: Hyperglycemic clamp |
| sildenafil Aim 2 | Experimental | sildenafil 25 mg p.o. tid Receives: Drug: Sildenafil; Diagnostic Test: Euglycemic clamp |
| placebo Aim 2 | Placebo comparator | matching placebo p.o. tid Receives: Drug: Placebo; Diagnostic Test: Euglycemic clamp |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin Secretion
in the group of subjects undergoing hyperglycemic clamp (Aim 1)
Measured: 2.5 hours after 3 months of therapy
Index of Tissue Sensitivity to Insulin
in the group of subjects undergoing hyperglycemic clamp (Aim 1), calculated by dividing the average glucose infusion rate during the last hour of the clamp by the average plasma insulin concentration during the same interval
Measured: 2.5 hours after 3 months of therapy
Glucose Infusion Rate
In the group of subjects undergoing euglycemic clamp (Aim 2)
Measured: 2.5 hours after 3 months of therapy
Secondary outcomes (2)
Fasting Plasma Glucose
Measured: 3 months
Blood Pressure
Systolic blood pressure
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2011 (estimated)
- Study startAug 2011
- Primary completionNov 2016
- Study completionNov 2016
Why it stopped: Aim 1 was stopped by DSMB. Aim 2 was stopped due to ending of funding.
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 (2)Papers the sponsor has linked to this study.
- Other trials for Impaired Glucose ToleranceStudies 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 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nancy J. Brown, Vanderbilt University
- Investigators
- Nancy J Brown, MD, Principal investigator, Vanderbilt University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01409993
- Sponsor's protocol ID
- 110206
- Status last verified
- Mar 2017
- First submitted
- 11 Jul 2011
- Last updated
- 17 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Ramirez CE, Nian H, Yu C, Gamboa JL, Luther JM, Brown NJ, Shibao CA. Treatment with Sildenafil Improves Insulin Sensitivity in Prediabetes: A Randomized, Controlled Trial. J Clin Endocrinol Metab. 2015 Dec;100(12):4533-40. doi: 10.1210/jc.2015-3415. Epub 2015 Nov 18.
PubMed 26580240Ramirez CE, Shuey MM, Milne GL, Gilbert K, Hui N, Yu C, Luther JM, Brown NJ. Arg287Gln variant of EPHX2 and epoxyeicosatrienoic acids are associated with insulin sensitivity in humans. Prostaglandins Other Lipid Mediat. 2014 Oct;113-115:38-44. doi: 10.1016/j.prostaglandins.2014.08.001. Epub 2014 Aug 28.
PubMed 25173047
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Renin-Angiotensin and Fibrinolysis in Humans: Effect of Long-Term PDE5 Inhibition on Glucose Homeostasis
- ClinicalTrials.gov ID
- NCT01409993
- Acronym / sponsor ID
- 110206
- Conditions
- Impaired Glucose Tolerance
- Keywords
- BMI greater than 25, Elevated fasting blood sugar (100-125mg/dL)
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Aim 1 was stopped by DSMB. Aim 2 was stopped due to ending of funding.
- Enrolment
- 78 participants (actual)
- Lead sponsor
- Vanderbilt UniversityUniversity, hospital or other
- Study start
- Aug 2011
- Primary completion
- Nov 2016 (actual)
- Study completion
- Nov 2016 (actual)
- First posted
- 4 Aug 2011 (estimated)
- Results
- Posted 17 Apr 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 determine the effect of chronic PDE5 inhibitor therapy on glucose metabolism in persons with prediabetes.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| sildenafil Aim 1 | Experimental | Drug: Sildenafil, Diagnostic Test: Hyperglycemic clampsildenafil 25 mg p.o. tid |
| placebo Aim 1 | Placebo comparator | Drug: Placebo, Diagnostic Test: Hyperglycemic clampmatching placebo p.o. tid |
| sildenafil Aim 2 | Experimental | Drug: Sildenafil, Diagnostic Test: Euglycemic clampsildenafil 25 mg p.o. tid |
| placebo Aim 2 | Placebo comparator | Drug: Placebo, Diagnostic Test: Euglycemic clampmatching placebo p.o. tid |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Age > 18 years and BMI > 25 kg/M2 (> 23 kg/M2 among Asian Americans) Elevated fasting plasma glucose (100-125 mg/dL) IGT (2 hour plasma glucose 140-199 mg/dL) OR metabolic syndrome and/or hemoglobin A1c 5.7-6.4%
Key exclusion criteria (25 listed)
- Diabetes type 1 or type 2, as defined by a fasting glucose of 126 mg/dL or greater, a two hour plasma glucose of 200 mg/dL or greater, or the use of anti-diabetic medication.
- The use of nitrates or any disease that might require the use of nitrates.
- The use of any potent CYP3A4 inhibitor.
- subjects who have participated in a weight-reduction program during the last 6 month or whose weight has increased or decreased more than 2 kg over the preceding 6 months.
- Pregnancy. Women of child-bearing potential will be required to have undergone tubal ligation or to be using barrier methods of birth control.
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 |
|---|---|---|
| SildenafilSildenafil 25 mg by mouth three times a day for three months | Drug | sildenafil Aim 1, sildenafil Aim 2 |
| PlaceboMatching placebo three times a day for three months | Drug | placebo Aim 1, placebo Aim 2 |
| Hyperglycemic clampSubjects with prediabetes will have a baseline hyperglycemic clamp (Aim 1) and then receive sildenafil or placebo for 3 months. Another hyperglycemic clamp will be performed followed by another 3 months off drug and an oral glucose tolerance test. | Diagnostic test | placebo Aim 1, sildenafil Aim 1 |
| Euglycemic clampSubjects with prediabetes will have a baseline euglycemic clamp (Aim 2) and then receive sildenafil or placebo for 3 months. Another euglycemic clamp will be performed followed by another 3 months off drug and an oral glucose tolerance test. | Diagnostic test | placebo Aim 2, sildenafil Aim 2 |
Primary outcome
Insulin Secretion
Time frame: 2.5 hours after 3 months of therapy
in the group of subjects undergoing hyperglycemic clamp (Aim 1)
Index of Tissue Sensitivity to Insulin
Time frame: 2.5 hours after 3 months of therapy
in the group of subjects undergoing hyperglycemic clamp (Aim 1), calculated by dividing the average glucose infusion rate during the last hour of the clamp by the average plasma insulin concentration during the same interval
Glucose Infusion Rate
Time frame: 2.5 hours after 3 months of therapy
In the group of subjects undergoing euglycemic clamp (Aim 2)
2 secondary outcomes
Fasting Plasma Glucose
Time frame: 3 months
Blood Pressure
Time frame: 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 26580240Ramirez CE, Nian H, Yu C, Gamboa JL, Luther JM, Brown NJ, Shibao CA. Treatment with Sildenafil Improves Insulin Sensitivity in Prediabetes: A Randomized, Controlled Trial. J Clin Endocrinol Metab. 2015 Dec;100(12):4533-40. doi: 10.1210/jc.2015-3415. Epub 2015 Nov 18.
- Derived from this study: PubMed 25173047Ramirez CE, Shuey MM, Milne GL, Gilbert K, Hui N, Yu C, Luther JM, Brown NJ. Arg287Gln variant of EPHX2 and epoxyeicosatrienoic acids are associated with insulin sensitivity in humans. Prostaglandins Other Lipid Mediat. 2014 Oct;113-115:38-44. doi: 10.1016/j.prostaglandins.2014.08.001. Epub 2014 Aug 28.
Related trials for Impaired Glucose Tolerance
Recruiting
Effects of Lean Pork Loin Intake on Protein Homeostasis and Glucose Regulation in Prediabetic Adults
Hyperglycaemia (Non Diabetic), Prediabetes
RecruitingObservational study
Food-i-Sense Analytics: Integrating AI Into Continuous Glucose Monitoring Data Analysis for Precision Nutrition.
Prediabetes (Insulin Resistance, Impaired Glucose Tolerance), Artificial Intelligence Mobile Application
Enrolling by invitationEarly Phase 1
Truway Diagnostic Tools in Primary Care
Chronic Disease, Type 2 Diabetes Mellitus (T2DM), Obesity, Overweight
Recruiting
CGM-Enhanced DPP to Prevent Type 2 Diabetes in Adults With Prediabetes
PreDiabetes
Active, not recruitingPhase 2
Extension Study to Evaluate the Safety of Long-Term Use of Relacorilant in Patients With Cushing Syndrome
Cushing Syndrome
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.
Nancy J Brown, MD principal investigator
Vanderbilt University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sildenafil, Hyperglycemic clamp and Euglycemic clamp in people with Impaired Glucose Tolerance, run by Vanderbilt University 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 1 inclusion and 25 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: stopped early, as of the sponsor's last update on 17 Apr 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 17 Apr 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?
Insulin Secretion (time frame: 2.5 hours after 3 months of therapy). The study lists 3 primary outcomes in all. 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 NCT01409993, which also lists 2 linked publications.
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 17 Apr 2017.