Metabolic SyndromePhase 4NCT02129725
Effect of Prolonged PDE-5 Inhibition on Insulin Signaling in Skeletal Muscle.
A Phase 4 study testing Sildenafil citrate in people with Metabolic Syndrome, run by Vanderbilt University Medical Center at 1 site in United States.
Trial summary
Our research proposal will determine if PDE-5 inhibition exerts a favorable effect on insulin signaling pathways in skeletal muscle of subjects with impaired fasting glucose and/or impaired glucose tolerance. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metabolic Syndrome
- What is being tested?
- Sildenafil citrate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2014to Dec 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) and ≤40kg/m2 Impaired fasting glucose (100-125mg/dL) and/or impaired glucose tolerance (2-hr plasma glucose 140-199 mg/dL) 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 or hormonal methods of birth control.
- Breast-feeding.
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- Cardiovascular disease such as myocardial infarction within 6 months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure, 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 on current inhaled corticosteroid therapy.
- Clinically significant gastrointestinal impairment that could interfere with drug absorption.
- Impaired hepatic function (aspartate amino transaminase and/or alanine amino transaminase >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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37232-6602
About this study
Official title: Renin- Angiotensin and Fibrinolysis Interaction in Humans: Effect of Long-term PDE-5 Inhibition on Glucose Homeostasis. Sub-study
Our research proposal will determine if PDE-5 inhibition exerts a favorable effect on insulin signaling pathways in skeletal muscle of subjects with impaired fasting glucose and/or impaired glucose tolerance.
Read the detailed description
Participants enrolled in the study titled " Renin-angiotensin and fibrinolysis interaction in humans: effect of long-term PDE5 inhibition on glucose Homeostasis, (Specific aim 2)" will be offered the opportunity to participate in this sub-study.
We will obtain skeletal muscle biopsies from 16 subjects who are enrolled in specific aim 2. Eight subjects will be in the sildenafil group and 8 subjects will be in the placebo group.
- Conditions
- Metabolic Syndrome
- Being tested
- Sildenafil citrate, Placebo Oral Capsule
- Medical subject headings
- Metabolic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sildenafil citrateDrug
Also called Viagra
Sildenafil citrate 25 mg, 1 capsule three times a day for 3 months
Placebo Oral CapsuleDrug
Also called placebo comparator
placebo capsules, 1 capsule po three times a day for 3 months
| Study group | Role | What they receive |
|---|---|---|
| sildenafil citrate | Experimental | In the parent study, subjects are randomized to sildenafil 25 mg tid. Receives: Drug: Sildenafil citrate |
| placebo oral capsule | Placebo comparator | In the parent study, subjects are randomized to matching placebo Receives: Drug: Placebo Oral Capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin-stimulated AKT Phosphorylation
measured using Western blot for pAkt and for total Akt from muscle biopsies obtained at the end of the baseline hyperinsulinemic clamp and the three-month hyperglycemic clamp.
The ratio of pAkt to Akt expression was calculated at each time point and the change in ratio from 0 to 3 months is presented.
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 posted2 May 2014 (estimated)
- Study startApr 2014
- Primary completionOct 2016
- Study completionDec 2016
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.
- Other trials for Metabolic SyndromeStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nancy J. Brown, Vanderbilt University Medical Center
- Investigators
- Nancy J Brown, MD, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02129725
- Sponsor's protocol ID
- 110206-substudy
- Status last verified
- Mar 2017
- First submitted
- 30 Apr 2014
- Last updated
- 19 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Renin- Angiotensin and Fibrinolysis Interaction in Humans: Effect of Long-term PDE-5 Inhibition on Glucose Homeostasis. Sub-study
- ClinicalTrials.gov ID
- NCT02129725
- Acronym / sponsor ID
- 110206-substudy
- Conditions
- Metabolic Syndrome
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Study start
- Apr 2014
- Primary completion
- Oct 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 2 May 2014 (estimated)
- Results
- Posted 19 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Our research proposal will determine if PDE-5 inhibition exerts a favorable effect on insulin signaling pathways in skeletal muscle of subjects with impaired fasting glucose and/or impaired glucose tolerance.
Detailed description
Participants enrolled in the study titled " Renin-angiotensin and fibrinolysis interaction in humans: effect of long-term PDE5 inhibition on glucose Homeostasis, (Specific aim 2)" will be offered the opportunity to participate in this sub-study.
We will obtain skeletal muscle biopsies from 16 subjects who are enrolled in specific aim 2. Eight subjects will be in the sildenafil group and 8 subjects will be in the placebo group.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| sildenafil citrate | Experimental | Drug: Sildenafil citrateIn the parent study, subjects are randomized to sildenafil 25 mg tid. |
| placebo oral capsule | Placebo comparator | Drug: Placebo Oral CapsuleIn the parent study, subjects are randomized to matching placebo |
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) and ≤40kg/m2 Impaired fasting glucose (100-125mg/dL) and/or impaired glucose tolerance (2-hr plasma glucose 140-199 mg/dL) and/or hemoglobin A1c 5.7-6.4%
Key exclusion criteria (23 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 or hormonal 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 |
|---|---|---|
| Sildenafil citrateAlso: ViagraSildenafil citrate 25 mg, 1 capsule three times a day for 3 months | Drug | sildenafil citrate |
| Placebo Oral CapsuleAlso: placebo comparatorplacebo capsules, 1 capsule po three times a day for 3 months | Drug | placebo oral capsule |
Primary outcome
Insulin-stimulated AKT Phosphorylation
Time frame: 3 months
measured using Western blot for pAkt and for total Akt from muscle biopsies obtained at the end of the baseline hyperinsulinemic clamp and the three-month hyperglycemic clamp. The ratio of pAkt to Akt expression was calculated at each time point and the change in ratio from 0 to 3 months is presented.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Nancy J Brown, MD principal investigator
Vanderbilt University Medical Center
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 citrate in people with Metabolic Syndrome, run by Vanderbilt University Medical Center 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 23 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 19 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 19 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-stimulated AKT Phosphorylation (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Apr 2017.