HIV Antiretroviral Drugs and Metabolism

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2011 by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:
NCT00525239
First received: September 4, 2007
Last updated: March 15, 2011
Last verified: March 2011
  Purpose

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.


Condition Intervention
HIV Infections
Drug: ritonavir, lopinavir/ritonavir, atazanavir/ritonavir, efavirenz

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label

Resource links provided by NLM:


Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:
  • Effect of HIV Protease Inhibitors on Glucose Metabolism by Hyperglycemic Clamp [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Effect of HIV Protease Inhibitors on Oral Glucose Tolerance Test [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 60
Study Start Date: March 2004
Estimated Study Completion Date: December 2010
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1: Ritonaivr
Pre and post ritonavir, lopinavir/ritonavir or atazanavir/ritonavir
Drug: ritonavir, lopinavir/ritonavir, atazanavir/ritonavir, efavirenz
100 mg, twice daily, for four weeks

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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 Coronary artery disease, peripheral vascular disease, impaired fasting glucose (glucose > 100 mg/dl), obese (BMI > 30), dyslipidemia (triglycerides > 190 mg/dl, LDL-C > 190), anemia (Hct < 39), hypertension (BP> 140/90 mmHg or on medication), blood pressure <100 mmHg, renal disease (creatinine > 1.6), LFT > ULN, or use within 30 days of systemic glucocorticoids, anabolic steroids, growth hormone, niacin, antipsychotics, or lipid lowering medications. Women will be tested for pregnancy immediately prior to each inpatient study and excluded if pregnant. For Specific Aim 2, additional exclusion criteria include history of depression requiring treatment, psychosis, hallucinations or delusions; use of cGMP specific phosphodiesterase 5 inhibitors (e.g., sildenafil) within 7 days of study; or history of adverse reaction to nitrates.

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00525239

Contacts
Contact: Carl Grunfeld, M.D., Ph.D. 415-750-2005 carl.grunfeld@ucsf.edu
Contact: Mae Pang, R.N. M.S.N 415-750-2005 miyin.pang@ucsf.edu

Locations
United States, California
Department of Veterans Affairs Medical Center Recruiting
San Francisco, California, United States, 94121
Contact: Mae Pang, RN, MSN    415-750-2005    miyin.pang@ucsf.edu   
Contact: Lyda Galvez    415-750-2005    lyda.galvez@va.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Carl Grunfeld, M.D., Ph.D. Northern California Institute for Research and Education
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Carl Grunfeld, M.D., Ph.D., Principal Investigator, Northern California Institute for Rerseach and Education
ClinicalTrials.gov Identifier: NCT00525239     History of Changes
Other Study ID Numbers: DK66999
Study First Received: September 4, 2007
Last Updated: March 15, 2011
Health Authority: United States: Federal Government

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
HIV-seronegative Volunteers
HIV-infected subjects starting an efavirenz-based regimen
Lipids
lipoproteins
VLDL
triglycerides
apo B100
HDL
apo A1
endothelial dysfunction
insulin secretion
hyperglycemic clamp
Treatment Experienced

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Atazanavir
Efavirenz
Lopinavir
Ritonavir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Protease Inhibitors
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014