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Statins for Pulmonary and Cardiac Complications of Chronic HIV - Coordinating Center (SPARC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01881971
Recruitment Status : Completed
First Posted : June 20, 2013
Last Update Posted : August 14, 2019
Information provided by (Responsible Party):
Alison Morris, University of Pittsburgh

Brief Summary:
Hypothesis: Statin therapy will decrease inflammation and slow progression of cardiopulmonary abnormalities in HIV.

Condition or disease Intervention/treatment Phase
HIV Seropositivity Drug: Placebo Drug: Rouvastatin calcium Early Phase 1

Detailed Description:

Growing evidence indicates that chronic obstructive pulmonary disease (COPD) is an important cause of respiratory impairment in HIV+ persons and will likely increase as the HIV+ population continues to age. In the HIV-uninfected population, COPD frequently co-exists with cardiac disease including atherosclerosis and pulmonary hypertension (PH). The investigators work has demonstrated that a syndrome of "cardiopulmonary dysfunction" exists even in non-smoking or antiretroviral-treated HIV+ individuals. The investigators have found that HIV+ individuals have a high prevalence of respiratory symptoms, airflow obstruction, and diffusing capacity (DLco) abnormalities that occur concurrently with cardiac co-morbidities, including radiographic measures of atherosclerosis and elevated echocardiographic pulmonary artery pressures. This syndrome is marked by inflammation with elevated levels of cytokines and hsCRP, peripheral T-cell activation, and increased sputum neutrophils as well as elevation of NT-proBNP, a marker of heart strain. Importantly, the investigators have shown that DLco impairment and elevated NT-proBNP are significant independent predictors of mortality in HIV, indicating that cardiopulmonary dysfunction is likely highly clinically relevant and identifies a vulnerable population in whom the investigators lack effective interventions.

Statins have anti-inflammatory effects in the lung and vasculature that might benefit cardiopulmonary dysfunction in HIV. These agents have a long history of clinical use in cardiovascular disease and are currently being investigated as disease-modifying drugs for HIV, COPD, and PH. In preliminary analyses, the investigators have found that HIV+ individuals who received statin therapy within the past year were significantly less likely to have impaired DLco and had lower pulmonary artery pressures, lower NT-proBNP, lower peripheral cytokines, and fewer sputum neutrophils despite being older and having a greater smoking history than those not using statins.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Multicenter, Prospective Adaptive Response Placebo-controlled Double-blind Study Comparing Effects of Rosuvastatin Versus Placebo
Study Start Date : May 2013
Actual Primary Completion Date : November 2015
Actual Study Completion Date : January 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Placebo Comparator: Placebo
manufactured sugar pill to mimic rouvastatin once a day for 24 weeks
Drug: Placebo
suger pill manufactured to mimic crestor pills

Experimental: Rouvastatin calcium
Rouvastatin calcium once a day by mouth for 24 weeks.
Drug: Rouvastatin calcium
Other Name: Crestor

Primary Outcome Measures :
  1. change in inflammatory markers - hsCRP [ Time Frame: 24 weeks ]
    To assess change in hsCRP after 24 weeks of therapy with rosuvastatin

Secondary Outcome Measures :
  1. effect of rosuvastatin on pulmonary and cardiac status by use of cIMT/FMD/ Vascular studies are a measure of preclinical atherosclerosis and predicts future cardiovascular events and mortality [ Time Frame: 2 years ]
    noninvsive Vascular cIMT, FMD and Glycocalyx will be measured at the beginning and at the end of the study

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • HIV-1 infection, documented in medical record at any time prior to study entry.
  • Men and women age18 years to 80 years.
  • Presence of COPD (FEV1/FVC<0.70 or DLco≤80% predicted)
  • No lipid-lowering medication (prescription or non-prescription) within 60 days prior to study entry. This includes all statin drugs, omega-3-fatty acids/fish oil (if dose > 1 g/day), red yeast rice (any dose), and niacin products (e.g., niacin, nicotinic acid, vitamin B3; if dose of >100 mg/day)
  • Normal liver and kidney function test at screening visit:
  • Liver function: ALT 7 to 55 U/L; AST 8 to 48 U/L; ALP 45 to 115 U/L; Bilirubin 0.1 to 1.0 mg/dL; GGT 9 to 48 U/L; LDH 122 to 222 umol/L; PT 8.3 to 10.8 seconds
  • Kidney function: BUN 8-20 mg/dl. Creatinine 0.8-1.2 mg/dl for males and 0.6-0.9 mg/dl for females. GFR normal results range from 90 - 120 mL/min/1.73 m2.) Participants will be on a stable ART regimen (i.e. no change in agents) with either suppressed HIV viral level or <50 viral level for at least 3 months.
  • If smoker, not planning on quitting smoking during the study period. If non-smoker, not planning on starting smoking during the study period.
  • Able to provide informed consent.
  • Able to participate in study procedures based on the investigator's assessment.
  • For women of reproductive potential, negative urine pregnancy test and willingness to use birth control during study period (see Contraception requirements).
  • Ability and willingness to complete all tests.
  • Participant in MACS, Women's Interagency Health Study, or Attendee of UPMC HIV / AIDS Program.

Exclusion Criteria:

  • Pregnancy or breast-feeding.
  • Known allergy/sensitivity or any hypersensitivity to HMG CoA reductase inhibitors, prior history of myopathy, rhabdomyolysis, or intolerance of statin therapy.
  • Currently receiving a statin or should be taking a statin based on clinical criteria.
  • Concurrent use of Coumadin.
  • History of liver disease.
  • Contraindication to pulmonary function testing (i.e. abdominal or cataract surgery within 3 months, recent myocardial infarction, etc.).
  • Diagnosis of asthma with normal diffusing capacity.
  • History of diabetes mellitus requiring medication of hemoglobin A1C>6.5% on screening laboratories.
  • Increasing respiratory symptoms or febrile (temperature >100.40F [380C]) within 4 weeks of study entry.
  • Hospitalization within 4 weeks prior to study entry.
  • Use of antibiotics within 4 weeks of study entry.
  • Uncontrolled hypertension at screening visit (systolic > 160 mm Hg or diastolic > 100 mm Hg) from an average of two or more readings. Subject may return for screening after blood pressure is controlled.
  • Active cancer requiring systemic chemotherapy or radiation.
  • Active infection of lungs, brain, or abdomen.
  • Use of anti-inflammatory agents (such as aspirin), immunomodulators (e.g., interleukins, interferons, cyclosporine) or immunosuppressive medications within 60 days prior to study entry. Routine vaccinations are allowed if administered at least 7 days prior to study entry.
  • Use of azole antifungals, erythromycin, or amiodarone.
  • More than weekly use of magnesium hydroxide.
  • The intention to quit smoking during the study period.
  • Alcoholism defined as >35 drinks per week or that will impair ability to complete study investigations in the opinion of the investigator.
  • Active (within the past 6 months) intravenous drug use or that will impair ability to complete study investigations in the opinion of the investigator.
  • Use of other investigational agents within 90 days of study entry or planning on entering another therapy trial during study period.
  • No use of inhaled corticosteroids (beta-agonists are allowed).
  • Viral load above 50 in past 3 months.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01881971

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United States, California
University of California, Los Angelos
Los Angeles, California, United States, 90095
University of California, SF
San Francisco, California, United States, 94118
United States, Pennsylvania
University of Pittsburgh department of medicine division of Pulmonary, Allergy and Critical Care medicine
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
Alison Morris
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Principal Investigator: Alison M Morris, MD, MS University of Pittsburgh

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Responsible Party: Alison Morris, Professor, University of Pittsburgh Identifier: NCT01881971     History of Changes
Other Study ID Numbers: PRO12100503
RFA-HL-12-034 ( Other Grant/Funding Number: NHLBI )
First Posted: June 20, 2013    Key Record Dates
Last Update Posted: August 14, 2019
Last Verified: August 2019
Keywords provided by Alison Morris, University of Pittsburgh:
no lipid lowering medication
normal liver and kidney function
on stable ART regimen
not pregnant
Additional relevant MeSH terms:
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HIV Seropositivity
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Calcium, Dietary
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Bone Density Conservation Agents