DiabetesNCT00259727
The Study of HIV Protease Inhibitors and Their Effects on Glucose Metabolism
An observational study of Diabetes and HIV Infections, run by US Department of Veterans Affairs at 1 site in United States.
Trial summary
The purpose of this study is to determine the mechanisms by which HIV protease inhibitors contribute to the development of diabetes in HIV-infected patients. The investigators propose that some HIV protease inhibitors impair insulin secretion and increase the production of glucose by the liver. Read more about this study
- Who is it for?
- Ages 18 to 72 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes, HIV Infections, Insulin Resistance
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2006to Sep 2008
- Phase
- Observational
- Are there results?
- None posted in the registry
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 72 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy, HIV-negative volunteers between the ages of 18-72 years
Who cannot join
- Any subject with states known to be associated with insulin resistance, such as impaired fasting glucose (glucose > 110 mg/dl), overweight (body mass index [BMI] > 27), dyslipidemia (triglycerides > 150 mg/dl), hypertension (blood pressure [BP] > 130/85 mmHg or on medication), renal disease, systemic use of glucocorticoids, growth hormone, niacin, or antipsychotics.
- Women will be tested for pregnancy immediately prior to study and excluded if pregnant.
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Medical Center, San Francisco
San Francisco, California, 94121
About this study
Official title: The Effects of HIV Protease Inhibitors on Glucose Metabolism
The purpose of this study is to determine the mechanisms by which HIV protease inhibitors contribute to the development of diabetes in HIV-infected patients. The investigators propose that some HIV protease inhibitors impair insulin secretion and increase the production of glucose by the liver.
Read the detailed description
HIV protease inhibitors (PIs) have been associated with type 2 diabetes. To design future HIV drugs that have have the least adverse metabolic effects, it is necessary to identify the disorders of glucose metabolism with PI therapy. Previously PIs have been shown to acutely induce insulin resistance in the periphery. Preliminary data show that PIs also impair insulin secretion and increase hepatic glucose production in humans. These lesions are key contributors to the development of type 2 diabetes. Due to the difficulty in separating out factors related to HIV infection from the direct effect of PIs, an effective design is to study HIV-negative subjects to define the direct effects of PIs on the liver and pancreas on glucose metabolism:
Specific Aim 1: To determine which PIs acutely inhibit insulin secretion in humans; randomized, double-blind, placebo-controlled trials will be performed on healthy normal volunteers given either a single dose of PI or placebo using the hyperglycemic clamp to assess insulin secretion in relation to insulin sensitivity.
Specific Aim 2: To determine which PIs acutely increase hepatic glucose production, glycogenolysis, and gluconeogenesis; measurements will be assessed in the fasting and hyperinsulinemic states using stable isotope analysis techniques. Samples have already been collected from double-blind, placebo-controlled trials of the effects of a single dose of PI on insulin sensitivity during the euglycemic hyperinsulinemic clamp.
Specific Aim 3: To determine the mechanism by which certain PIs increase hepatic glucose production; an infusion of somatostatin during the fasting state and hyperinsulinemic state will be used to suppress the effects of glucagon. Subjects will undergo a randomized, double-blind, placebo-controlled trial of a single dose of PI or placebo on insulin sensitivity using the euglycemic hyperinsulinemic clamp. Somatostatin, glucagon, and growth hormone will be infused before and during the clamp study. Hepatic glucose production, glycogenolysis, and gluconeogenesis will be assessed using stable isotope tracer techniques. Results will be compared to PIs acutely given in the absence of somatostatin, as stated in Specific Aim 2.
Determination of the effects of PI therapy allows clinicians to identify patients who may be at particular risk for developing diabetes on certain PIs and treat them more effectively. In the future, drugs for the treatment of HIV can be developed that avoid these disorders of glucose metabolism.
- Conditions
- Diabetes, HIV Infections, Insulin Resistance
- Keywords
- Amprenavir, Glucagon, HIV Protease inhibitors, Indinavir, Lopinavir, Ritonavir
- Medical subject headings
- Diabetes Mellitus, HIV Infections, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin secretion after a single dose of HIV protease inhibitor versus placebo (insulin secretion assessed by using the hyperglycemic clamp technique)
Secondary outcomes (2)
Hepatic glucose production, glycogenolysis, and gluconeogenesis after a single dose of HIV protease inhibitor versus placebo (stable isotope analysis with mass isotopic distribution analysis)
Hepatic glucose production during a somatostatin infusion in the fasting and hyperinsulinemic state after a single dose of HIV protease inhibitor
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2005 (estimated)
- Study startJan 2006
- Study completionSep 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for DiabetesStudies 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
- Observational
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- US Department of Veterans Affairs
- Sponsor type
- US federal agency
- Investigators
- Grace Lee, MD, Principal investigator, VA Medical Center, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00259727
- Sponsor's protocol ID
- RCD-005-05S
- Status last verified
- Mar 2009
- First submitted
- 28 Nov 2005
- Last updated
- 30 Sep 2009
- Results posted
- No
Publications
Noor MA, Lo JC, Mulligan K, Schwarz JM, Halvorsen RA, Schambelan M, Grunfeld C. Metabolic effects of indinavir in healthy HIV-seronegative men. AIDS. 2001 May 4;15(7):F11-8. doi: 10.1097/00002030-200105040-00001.
PubMed 11399973Noor MA, Seneviratne T, Aweeka FT, Lo JC, Schwarz JM, Mulligan K, Schambelan M, Grunfeld C. Indinavir acutely inhibits insulin-stimulated glucose disposal in humans: a randomized, placebo-controlled study. AIDS. 2002 Mar 29;16(5):F1-8. doi: 10.1097/00002030-200203290-00002.
PubMed 11964551Woerle HJ, Mariuz PR, Meyer C, Reichman RC, Popa EM, Dostou JM, Welle SL, Gerich JE. Mechanisms for the deterioration in glucose tolerance associated with HIV protease inhibitor regimens. Diabetes. 2003 Apr;52(4):918-25. doi: 10.2337/diabetes.52.4.918.
PubMed 12663461Lee GA, Seneviratne T, Noor MA, Lo JC, Schwarz JM, Aweeka FT, Mulligan K, Schambelan M, Grunfeld C. The metabolic effects of lopinavir/ritonavir in HIV-negative men. AIDS. 2004 Mar 5;18(4):641-9. doi: 10.1097/00002030-200403050-00008.
PubMed 15090769Lee GA, Mafong DD, Noor MA, Lo JC, Mulligan K, Schwarz JM, Schambelan M, Grunfeld C. HIV protease inhibitors increase adiponectin levels in HIV-negative men. J Acquir Immune Defic Syndr. 2004 May 1;36(1):645-7. doi: 10.1097/00126334-200405010-00017. No abstract available.
PubMed 15097312Schwarz JM, Lee GA, Park S, Noor MA, Lee J, Wen M, Lo JC, Mulligan K, Schambelan M, Grunfeld C. Indinavir increases glucose production in healthy HIV-negative men. AIDS. 2004 Sep 3;18(13):1852-4. doi: 10.1097/00002030-200409030-00017.
PubMed 15316349
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of HIV Protease Inhibitors on Glucose Metabolism
- ClinicalTrials.gov ID
- NCT00259727
- Acronym / sponsor ID
- RCD-005-05S
- Conditions
- Diabetes, HIV Infections, Insulin Resistance
- Keywords
- Amprenavir, Glucagon, HIV Protease inhibitors, Indinavir, Lopinavir, Ritonavir
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- US Department of Veterans AffairsUS federal agency
- Study start
- Jan 2006
- Study completion
- Sep 2008 (actual)
- First posted
- 29 Nov 2005 (estimated)
- Results
- Not posted in the source record
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 mechanisms by which HIV protease inhibitors contribute to the development of diabetes in HIV-infected patients. The investigators propose that some HIV protease inhibitors impair insulin secretion and increase the production of glucose by the liver.
Detailed description
HIV protease inhibitors (PIs) have been associated with type 2 diabetes. To design future HIV drugs that have have the least adverse metabolic effects, it is necessary to identify the disorders of glucose metabolism with PI therapy. Previously PIs have been shown to acutely induce insulin resistance in the periphery. Preliminary data show that PIs also impair insulin secretion and increase hepatic glucose production in humans. These lesions are key contributors to the development of type 2 diabetes. Due to the difficulty in separating out factors related to HIV infection from the direct effect of PIs, an effective design is to study HIV-negative subjects to define the direct effects of PIs on the liver and pancreas on glucose metabolism:
Specific Aim 1: To determine which PIs acutely inhibit insulin secretion in humans; randomized, double-blind, placebo-controlled trials will be performed on healthy normal volunteers given either a single dose of PI or placebo using the hyperglycemic clamp to assess insulin secretion in relation to insulin sensitivity.
Specific Aim 2: To determine which PIs acutely increase hepatic glucose production, glycogenolysis, and gluconeogenesis; measurements will be assessed in the fasting and hyperinsulinemic states using stable isotope analysis techniques. Samples have already been collected from double-blind, placebo-controlled trials of the effects of a single dose of PI on insulin sensitivity during the euglycemic hyperinsulinemic clamp.
Specific Aim 3: To determine the mechanism by which certain PIs increase hepatic glucose production; an infusion of somatostatin during the fasting state and hyperinsulinemic state will be used to suppress the effects of glucagon. Subjects will undergo a randomized, double-blind, placebo-controlled trial of a single dose of PI or placebo on insulin sensitivity using the euglycemic hyperinsulinemic clamp. Somatostatin, glucagon, and growth hormone will be infused before and during the clamp study. Hepatic glucose production, glycogenolysis, and gluconeogenesis will be assessed using stable isotope tracer techniques. Results will be compared to PIs acutely given in the absence of somatostatin, as stated in Specific Aim 2.
Determination of the effects of PI therapy allows clinicians to identify patients who may be at particular risk for developing diabetes on certain PIs and treat them more effectively. In the future, drugs for the treatment of HIV can be developed that avoid these disorders of glucose metabolism.
Study design
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | – | – |
Who may qualify
- Ages
- 18 to 72 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Healthy, HIV-negative volunteers between the ages of 18-72 years
Key exclusion criteria (2 listed)
- Any subject with states known to be associated with insulin resistance, such as impaired fasting glucose (glucose > 110 mg/dl), overweight (body mass index [BMI] > 27), dyslipidemia (triglycerides > 150 mg/dl), hypertension (blood pressure [BP] > 130/85 mmHg or on medication), renal disease, systemic use of glucocorticoids, growth hormone, niacin, or antipsychotics.
- Women will be tested for pregnancy immediately prior to study and excluded if pregnant.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Insulin secretion after a single dose of HIV protease inhibitor versus placebo (insulin secretion assessed by using the hyperglycemic clamp technique)
2 secondary outcomes
Hepatic glucose production, glycogenolysis, and gluconeogenesis after a single dose of HIV protease inhibitor versus placebo (stable isotope analysis with mass isotopic distribution analysis)
Hepatic glucose production during a somatostatin infusion in the fasting and hyperinsulinemic state after a single dose of HIV protease inhibitor
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2009.
- Results publication: PubMed 11399973Noor MA, Lo JC, Mulligan K, Schwarz JM, Halvorsen RA, Schambelan M, Grunfeld C. Metabolic effects of indinavir in healthy HIV-seronegative men. AIDS. 2001 May 4;15(7):F11-8. doi: 10.1097/00002030-200105040-00001.
- Results publication: PubMed 11964551Noor MA, Seneviratne T, Aweeka FT, Lo JC, Schwarz JM, Mulligan K, Schambelan M, Grunfeld C. Indinavir acutely inhibits insulin-stimulated glucose disposal in humans: a randomized, placebo-controlled study. AIDS. 2002 Mar 29;16(5):F1-8. doi: 10.1097/00002030-200203290-00002.
- Results publication: PubMed 12663461Woerle HJ, Mariuz PR, Meyer C, Reichman RC, Popa EM, Dostou JM, Welle SL, Gerich JE. Mechanisms for the deterioration in glucose tolerance associated with HIV protease inhibitor regimens. Diabetes. 2003 Apr;52(4):918-25. doi: 10.2337/diabetes.52.4.918.
- Results publication: PubMed 15090769Lee GA, Seneviratne T, Noor MA, Lo JC, Schwarz JM, Aweeka FT, Mulligan K, Schambelan M, Grunfeld C. The metabolic effects of lopinavir/ritonavir in HIV-negative men. AIDS. 2004 Mar 5;18(4):641-9. doi: 10.1097/00002030-200403050-00008.
- Results publication: PubMed 15097312Lee GA, Mafong DD, Noor MA, Lo JC, Mulligan K, Schwarz JM, Schambelan M, Grunfeld C. HIV protease inhibitors increase adiponectin levels in HIV-negative men. J Acquir Immune Defic Syndr. 2004 May 1;36(1):645-7. doi: 10.1097/00126334-200405010-00017. No abstract available.
- Results publication: PubMed 15316349Schwarz JM, Lee GA, Park S, Noor MA, Lee J, Wen M, Lo JC, Mulligan K, Schambelan M, Grunfeld C. Indinavir increases glucose production in healthy HIV-negative men. AIDS. 2004 Sep 3;18(13):1852-4. doi: 10.1097/00002030-200409030-00017.
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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.
Grace Lee, MD principal investigator
VA Medical Center, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Diabetes and HIV Infections, run by US Department of Veterans Affairs 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 2 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 Sep 2009. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 after a single dose of HIV protease inhibitor versus placebo (insulin secretion assessed by using the hyperglycemic clamp technique). 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 NCT00259727, which also lists 6 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 30 Sep 2009.