Insulin ResistancePhase 1/2NCT03012386
CD36 in Nutrient Delivery and Its Dysfunction
A Phase 1/2 study testing Sildenafil Citrate in G allele carrier and Sildenafil Citrate in non G allele carrier in people with Insulin Resistance and Endothelial Dysfunction, run by Vanderbilt University Medical Center at 1 site in United States.
Trial summary
This proposal will test the hypothesis that chronic treatment with sildenafil with and without the use of nitric oxide substrate, L-arginine, protects against fatty acid induced impairment of endothelial function, improves insulin-stimulated microvascular recruitment, insulin sensitivity and glucose uptake in CD36… Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Insulin Resistance, Endothelial Dysfunction
- What is being tested?
- Sildenafil Citrate in G allele carrier and Sildenafil Citrate in non G allele carrier
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2017to 31 Jul 2021
- Phase
- Phase 1/2
- 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
- African American men and women.
- Age 18-50 years
- BMI 25-40 kg/m2
Who cannot join
- Diabetes type 1 or type 2, as defined by a FPG > 126 mg/dL a two-hour plasma glucose > 200 mg/dL, or the use of anti-diabetic medication
- Pulmonary hypertension
- Use of a PDE5 inhibitor for erectile dysfunction
- Pregnancy or breast-feeding. Women of child-bearing potential will be required to have undergone tubal ligation or to be using an oral contraceptive or barrier methods of birth control.
- Cardiovascular disease such as myocardial infarction, presence of angina pectoris, significant arrhythmia, congestive heart failure (left ventricular hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis or hypertrophic cardiomyopathy
- History of serious neurologic disease such as cerebral hemorrhage, stroke, or transient ischemic attack
Show all 12Show fewer
- History or presence of immunological or hematological disorders
- 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)
- History of alcohol or drug abuse
- Mental conditions rendering a 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, unlikelihood of completing the study, and investigator discretion
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
Official title: Role of CD36 in Nutrient Delivery and Its Dysfunction in African Americans
This proposal will test the hypothesis that chronic treatment with sildenafil with and without the use of nitric oxide substrate, L-arginine, protects against fatty acid induced impairment of endothelial function, improves insulin-stimulated microvascular recruitment, insulin sensitivity and glucose uptake in CD36 rs3211938 G-allele carriers.
Read the detailed description
Subjects carrying the G-allele of CD36 coding SNP rs3211938 that results in 50% reduction of CD36 levels in ~25% of African Americans have endothelial dysfunction. Endothelial dysfunction results in impairment of insulin's vascular actions and eventually reduced insulin sensitivity. Insulin induces microvascular recruitment via stimulation of nitric oxide(NO)-cGMP pathway, which facilitates nutrient flux, e.g., glucose to skeletal muscle. Elevated fatty acids impair insulin-stimulated microvascular recruitment and reduce insulin sensitivity. Chronic treatment with sildenafil increases vascularity and muscle glucose uptake in high fat fed mice. In humans, Drs. Shibao (PI) recently reported that a 3-month treatment with sildenafil improves insulin sensitivity in patients with impaired glucose tolerance. More relevant to this project, endothelial dysfunction improved after 4-week treatment with sildenafil in G-allele carriers. This proposal will test the hypothesis that chronic treatment with sildenafil with and without the use of NO substrate, L-arginine, protects against fatty acids induced impairment of endothelial function, improves insulin-stimulated microvascular.
The protocol design was changed to single arm design.
- Conditions
- Insulin Resistance, Endothelial Dysfunction
- Being tested
- Sildenafil Citrate in G allele carrier, Sildenafil Citrate in non G allele carrier
- Keywords
- CD36, Endothelial dysfunction, African Americans
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sildenafil Citrate in G allele carrierDrug
Also called viagra, revatio,
chronic use of phosphodiesterase 5 inhibitor in G allele carrier
Sildenafil Citrate in non G allele carrierDrug
Also called viagra, revatio
chronic use of phosphodiesterase 5 inhibitor in Non G allele carrier
| Study group | Role | What they receive |
|---|---|---|
| Sildenafil citrate | Experimental | Sildenafil citrate 20 mg three times a day Receives: Drug: Sildenafil Citrate in G allele carrier; Drug: Sildenafil Citrate in non G allele carrier |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Microvascular Blood Volume (MBV) During Insulin Infusion
Insulin induces microvascular recruitment. Changes in MBV during Insulin infusion signifies insulin sensitivity.
MBV is measured in the forearm brachioradialis muscle with contrast enhanced ultrasonography during minutes 120-150 of a hyperinsulinaemic euglycaemic (HIE) clamp (insulin infusion rate up to 80 mU/m2.min-1 ). In the last 30 minutes, L-arginine was infused (10 mg/kg/min for 30 minutes) and ultrasound measurements were repeated upon infusion completion (approximately minute 180).
Measured: Baseline to end of procedure (approximately 180 minutes)
Change in Microvascular Blood Volume (MBV) During Insulin Infusion After 4 Weeks of Sildenafil Treatment in Both Groups
Chronic treatment with sildenafil increases vascularity and muscle glucose uptake. Changes in MBV during Insulin infusion signifies insulin sensitivity .
Insulin sensitivity was tested after 4 weeks of treatment with Sildenafil in both groups. Subjects receive IV infusion of 20% Intralipid (45ml/h) and heparin (200 units/hr). MBV is measured in the forearm brachioradialis muscle with contrast enhanced ultrasonography during minutes 120-150 of a HIE clamp (insulin infusion rate up to 80 mU/m2.min-1 ) In the last 30 minutes, L-arginine was infused (10 mg/kg/min for 30 minutes) and ultrasound measurements were repeated upon infusion completion (approximately minute 180).
Measured: Baseline to 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2017 (estimated)
- Study startJan 2017
- Primary completionJul 2021
- Study completion31 Jul 2021
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 Insulin ResistanceStudies 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 1/2
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Washington University School of Medicine
- Responsible party
- Principal investigator, Cyndya Shibao, MD, Vanderbilt University Medical Center
- Investigators
- Cyndya Shibao, MD, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03012386
- Sponsor's protocol ID
- 160955
- Status last verified
- Nov 2022
- First submitted
- 3 Jan 2017
- Last updated
- 30 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Shibao CA, Peche VS, Pietka TA, Samovski D, Williams IM, Abumrad NN, Gamazon ER, Goldberg IJ, Wasserman DH, Abumrad NA. Microvascular insulin resistance with enhanced muscle glucose disposal in CD36 deficiency. Diabetologia. 2025 Mar;68(3):662-675. doi: 10.1007/s00125-024-06292-4. Epub 2024 Nov 6.
PubMed 39503770
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of CD36 in Nutrient Delivery and Its Dysfunction in African Americans
- ClinicalTrials.gov ID
- NCT03012386
- Acronym / sponsor ID
- 160955
- Conditions
- Insulin Resistance, Endothelial Dysfunction
- Keywords
- CD36, Endothelial dysfunction, African Americans
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Collaborators
- Washington University School of Medicine
- Study start
- Jan 2017 (actual)
- Primary completion
- Jul 2021 (actual)
- Study completion
- 31 Jul 2021 (actual)
- First posted
- 6 Jan 2017 (estimated)
- Results
- Posted 30 Nov 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This proposal will test the hypothesis that chronic treatment with sildenafil with and without the use of nitric oxide substrate, L-arginine, protects against fatty acid induced impairment of endothelial function, improves insulin-stimulated microvascular recruitment, insulin sensitivity and glucose uptake in CD36 rs3211938 G-allele carriers.
Detailed description
Subjects carrying the G-allele of CD36 coding SNP rs3211938 that results in 50% reduction of CD36 levels in ~25% of African Americans have endothelial dysfunction. Endothelial dysfunction results in impairment of insulin's vascular actions and eventually reduced insulin sensitivity. Insulin induces microvascular recruitment via stimulation of nitric oxide(NO)-cGMP pathway, which facilitates nutrient flux, e.g., glucose to skeletal muscle. Elevated fatty acids impair insulin-stimulated microvascular recruitment and reduce insulin sensitivity. Chronic treatment with sildenafil increases vascularity and muscle glucose uptake in high fat fed mice. In humans, Drs. Shibao (PI) recently reported that a 3-month treatment with sildenafil improves insulin sensitivity in patients with impaired glucose tolerance. More relevant to this project, endothelial dysfunction improved after 4-week treatment with sildenafil in G-allele carriers. This proposal will test the hypothesis that chronic treatment with sildenafil with and without the use of NO substrate, L-arginine, protects against fatty acids induced impairment of endothelial function, improves insulin-stimulated microvascular.
The protocol design was changed to single arm design.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sildenafil citrate | Experimental | Drug: Sildenafil Citrate in G allele carrier, Drug: Sildenafil Citrate in non G allele carrierSildenafil citrate 20 mg three times a day |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- African American men and women.
- Age 18-50 years
- BMI 25-40 kg/m2
Key exclusion criteria (12 listed)
- Diabetes type 1 or type 2, as defined by a FPG > 126 mg/dL a two-hour plasma glucose > 200 mg/dL, or the use of anti-diabetic medication
- Pulmonary hypertension
- Use of a PDE5 inhibitor for erectile dysfunction
- Pregnancy or breast-feeding. Women of child-bearing potential will be required to have undergone tubal ligation or to be using an oral contraceptive or barrier methods of birth control.
- Cardiovascular disease such as myocardial infarction, presence of angina pectoris, significant arrhythmia, congestive heart failure (left ventricular hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis or hypertrophic cardiomyopathy
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 Citrate in G allele carrierAlso: viagra, revatio,chronic use of phosphodiesterase 5 inhibitor in G allele carrier | Drug | Sildenafil citrate |
| Sildenafil Citrate in non G allele carrierAlso: viagra, revatiochronic use of phosphodiesterase 5 inhibitor in Non G allele carrier | Drug | Sildenafil citrate |
Primary outcome
Change in Microvascular Blood Volume (MBV) During Insulin Infusion
Time frame: Baseline to end of procedure (approximately 180 minutes)
Insulin induces microvascular recruitment. Changes in MBV during Insulin infusion signifies insulin sensitivity. MBV is measured in the forearm brachioradialis muscle with contrast enhanced ultrasonography during minutes 120-150 of a hyperinsulinaemic euglycaemic (HIE) clamp (insulin infusion rate up to 80 mU/m2.min-1 ). In the last 30 minutes, L-arginine was infused (10 mg/kg/min for 30 minutes) and ultrasound measurements were repeated upon infusion completion (approximately minute 180).
Change in Microvascular Blood Volume (MBV) During Insulin Infusion After 4 Weeks of Sildenafil Treatment in Both Groups
Time frame: Baseline to 4 weeks
Chronic treatment with sildenafil increases vascularity and muscle glucose uptake. Changes in MBV during Insulin infusion signifies insulin sensitivity . Insulin sensitivity was tested after 4 weeks of treatment with Sildenafil in both groups. Subjects receive IV infusion of 20% Intralipid (45ml/h) and heparin (200 units/hr). MBV is measured in the forearm brachioradialis muscle with contrast enhanced ultrasonography during minutes 120-150 of a HIE clamp (insulin infusion rate up to 80 mU/m2.min-1 ) In the last 30 minutes, L-arginine was infused (10 mg/kg/min for 30 minutes) and ultrasound measurements were repeated upon infusion completion (approximately minute 180).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39503770Shibao CA, Peche VS, Pietka TA, Samovski D, Williams IM, Abumrad NN, Gamazon ER, Goldberg IJ, Wasserman DH, Abumrad NA. Microvascular insulin resistance with enhanced muscle glucose disposal in CD36 deficiency. Diabetologia. 2025 Mar;68(3):662-675. doi: 10.1007/s00125-024-06292-4. Epub 2024 Nov 6.
- 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.
Cyndya Shibao, 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 1/2 study testing Sildenafil Citrate in G allele carrier and Sildenafil Citrate in non G allele carrier in people with Insulin Resistance and Endothelial Dysfunction, 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 3 inclusion and 12 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 Nov 2022. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Nov 2022). 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 Microvascular Blood Volume (MBV) During Insulin Infusion (time frame: Baseline to end of procedure (approximately 180 minutes)). The study lists 2 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 NCT03012386, 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 Nov 2022.