HIV Antiretroviral Drugs and Metabolism

NCT ID: NCT00525239

Last Updated: 2011-03-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-03-31

Study Completion Date

2010-12-31

Brief Summary

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Hypothesis 1: Ritonavir-based regimens increase triglycerides and VLDL by both increasing VLDL production and decreasing VLDL clearance.

Specific Aim 1A: To quantify the effect of ritonavir on VLDL production and clearance using stable isotope turnover and other clearance methods.

Specific Aim 1B: To determine the composition of the triglyceride rich particles.

Protocol 1: The effects of ritonavir-based regimens on VLDL production, VLDL clearance and triglyceride-rich lipoprotein composition in healthy normal volunteers. HIV-seronegative volunteers will be studied before and at the end of four weeks of taking ritonavir, lopinavir/ritonavir or atazanavir/ritonavir.

Hypothesis 2: NNRTI drugs do not increase HDL by increasing apo AI production, but rather by decreasing apo AI clearance, prolonging time in circulation.

Specific Aim 2A: To determine the composition of HDL before and after NNRTI and assess its function.

Specific Aim 2B: To quantify the effect of NNRTI on apo AI production and clearance using stable isotopes.

Specific Aim 2C: To determine if the NNRTI induced increase in HDL is accompanied by improvement in flow mediated vasodilation and circulating markers of endothelial function Protocol 2A: The effects of efavirenz on HDL composition, HDL function, apo AI production, apo AI clearance, flow mediated vasodilation and circulating markers of endothelial dysfunction in healthy normal volunteers. HIV-seronegative volunteers will be studied before and at the end of six weeks of taking efavirenz.

Protocol 2B: The effects of starting an efavirenz-based regimen on HDL composition, HDL function, apo AI production, apo AI clearance, flow mediated vasodilation and circulating markers of endothelial dysfunction in patients with HIV infection. HIV-infected patients whose care providers have prescribed an efavirenz-based regimen will be studied before and after six weeks of starting efavirenz.

Hypothesis 3: Ritonavir-based PI regimens impair insulin secretion. Specific Aim 3: To determine which ritonavir-based PI regimens alter insulin secretion.

Protocol 3: The effects of ritonavir-based regimens on insulin secretion in healthy normal volunteers. HIV-seronegative volunteers will be studied before and at the end of four weeks of taking ritonavir, lopinavir/ritonavir or atazanavir/ritonavir.

Detailed Description

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Conditions

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HIV Infections

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Blinding Strategy

NONE

Study Groups

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1: Ritonaivr

Pre and post ritonavir, lopinavir/ritonavir or atazanavir/ritonavir

Group Type EXPERIMENTAL

ritonavir, lopinavir/ritonavir, atazanavir/ritonavir, efavirenz

Intervention Type DRUG

100 mg, twice daily, for four weeks

Interventions

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ritonavir, lopinavir/ritonavir, atazanavir/ritonavir, efavirenz

100 mg, twice daily, for four weeks

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

Protocols 1, 2A and 3 HIV negative, healthy normal volunteers, age \> 18 years old.

Protocol 2B HIV-infected subjects, age \> 18 years old and documented to have HIV-1 infection for ≥ 6 months, being started on efavirenz by their health care provider.

Exclusion Criteria

Protocols 1, 2A and 3 Currently on an NNRTI, coronary artery disease, peripheral vascular disease, recent opportunistic infection (within two months), impaired fasting glucose (glucose \> 100 mg/dl) or diabetes, anemia (Hct \< 39), hypertension (BP \> 140/90 mmHg or on medication), blood pressure \<100 mmHg, renal disease (Creatinine \> 1.6), LFT \> 2x ULN, use of cGMP specific phosphodiesterase 5 inhibitors (e.g., sildenafil) within 7 days of study, history of adverse reaction to nitrates, use within 30 days of anabolic steroids, systemic glucocorticoids, growth hormone, niacin, antipsychotics, or lipid lowering medications. Women will be tested for pregnancy immediately prior to each inpatient study and excluded if pregnant
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role lead

Responsible Party

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Northern California Institute for Rerseach and Education

Principal Investigators

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Carl Grunfeld, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Northern California Institute for Research and Education

Locations

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Department of Veterans Affairs Medical Center

San Francisco, California, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Carl Grunfeld, M.D., Ph.D.

Role: CONTACT

415-750-2005

Mae Pang, R.N. M.S.N

Role: CONTACT

415-750-2005

Facility Contacts

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Mae Pang, RN, MSN

Role: primary

415-750-2005

Lyda Galvez

Role: backup

415-750-2005

References

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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.

Reference Type RESULT
PMID: 11399973 (View on PubMed)

Noor 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.

Reference Type RESULT
PMID: 11964551 (View on PubMed)

Lee 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.

Reference Type RESULT
PMID: 15090769 (View on PubMed)

Lee 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.

Reference Type RESULT
PMID: 15097312 (View on PubMed)

Schwarz 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.

Reference Type RESULT
PMID: 15316349 (View on PubMed)

Lee GA, Rao MN, Grunfeld C. The effects of HIV protease inhibitors on carbohydrate and lipid metabolism. Curr HIV/AIDS Rep. 2005 Feb;2(1):39-50. doi: 10.1007/s11904-996-0008-z.

Reference Type RESULT
PMID: 16091248 (View on PubMed)

Lee GA, Lo JC, Aweeka F, Schwarz JM, Mulligan K, Schambelan M, Grunfeld C. Single-dose lopinavir-ritonavir acutely inhibits insulin-mediated glucose disposal in healthy volunteers. Clin Infect Dis. 2006 Sep 1;43(5):658-60. doi: 10.1086/505974. Epub 2006 Jul 26.

Reference Type RESULT
PMID: 16886163 (View on PubMed)

Lee GA, Rao M, Mulligan K, Lo JC, Aweeka F, Schwarz JM, Schambelan M, Grunfeld C. Effects of ritonavir and amprenavir on insulin sensitivity in healthy volunteers. AIDS. 2007 Oct 18;21(16):2183-90. doi: 10.1097/QAD.0b013e32826fbc54.

Reference Type RESULT
PMID: 18090045 (View on PubMed)

Taylor SA, Lee GA, Pao VY, Anthonypillai J, Aweeka FT, Schwarz JM, Mulligan K, Schambelan M, Grunfeld C. Boosting dose ritonavir does not alter peripheral insulin sensitivity in healthy HIV-seronegative volunteers. J Acquir Immune Defic Syndr. 2010 Nov;55(3):361-4. doi: 10.1097/QAI.0b013e3181e6a7d9.

Reference Type DERIVED
PMID: 20595906 (View on PubMed)

Pao VY, Lee GA, Taylor S, Aweeka FT, Schwarz JM, Mulligan K, Schambelan M, Grunfeld C. The protease inhibitor combination lopinavir/ritonavir does not decrease insulin secretion in healthy, HIV-seronegative volunteers. AIDS. 2010 Jan 16;24(2):265-70. doi: 10.1097/QAD.0b013e328333af1c.

Reference Type DERIVED
PMID: 19890203 (View on PubMed)

Other Identifiers

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DK66999

Identifier Type: -

Identifier Source: org_study_id

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