Minocycline for the Treatment of Decreased Mental Function in HIV-Infected Adults

NCT ID: NCT00361257

Last Updated: 2016-02-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 107 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-03-31
• Study Completion Date: 2010-01-31

Brief Summary

The purpose of this study is to determine the effectiveness of minocycline, an antibiotic, in lessening the decreased mental function sometimes caused by anti-HIV drugs.

Detailed Description

Cognitive impairment, including disabling cognitive, behavioral, and social dysfunction, continues to be a major problem faced by HIV-infected people taking antiretroviral therapy (ART). Research is needed to develop treatment that can be given alongside ART to prevent or lessen cognitive impairment caused by ART. Minocycline, an antibiotic commonly used for the treatment of acne and rheumatoid arthritis, has demonstrated anti-inflammatory and neuroprotective properties in previous studies. This study will evaluate the effectiveness of 24-week therapy with minocycline in lessening the cognitive impairment of HIV infected adults taking ART.

This study will last at least 24 weeks and has two steps. Patients will be stratified by HIV viral load and their neurocognitive state at study screening. In Step I, patients will be randomly assigned to one of two groups. Group 1 participants will receive twice-daily minocycline for 24 weeks; Group 2 participants will receive placebo. At the end of Phase I, study participants will be offered to enter Step II; all participants in Step II will receive twice-daily minocycline for an additional 24 weeks.

There will be a total of 8 study visits: 5 visits for Step I (including the entry visit) and 3 visits for Step II. Medical history will occur at all visits. Blood collection will occur at all visits. Participants who have positive nonreactive rapid plasma regain (RPR) values at screening will have mandatory lumbar punctures; for those with negative serum RPR results lumbar punctures are optional. Participants who test positive for syphilis will also have a lumbar puncture at their discretion to determine if syphilis has affected the brain. A neurological exam, other neuropsychological, dementia, and depression scale assessments, and urine collection will occur at most visits. Patients will be asked to complete a questionnaire on daily living at study entry and Weeks 12 and 24. Patients who have a lumbar puncture at Week 24 will receive a phone call 2 to 5 days after the procedure to report any adverse effects. Some participants may also have an electrocardiogram (ECG) during the study. For participants not on atazanavir some procedures and sample collections are optional.

Conditions

HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Arm 1: Minocycline

100 mg orally every 12 hours

Group Type: EXPERIMENTAL

Minocycline

Intervention Type: DRUG

Tetracycline antibiotic, 100 mg taken orally every 12 hours

Arm 2: Matching placebo

orally every 12 hours

Group Type: PLACEBO_COMPARATOR

Placebo (Tetracycline)

Intervention Type: DRUG

Tetracycline antibiotic placebo, orally every 12 hours

Interventions

Minocycline

Tetracycline antibiotic, 100 mg taken orally every 12 hours

Intervention Type: DRUG

Placebo (Tetracycline)

Tetracycline antibiotic placebo, orally every 12 hours

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• HIV infected
• Currently on a stable ART regimen for at least 16 consecutive weeks prior to study entry. Participants whose regimens have changed with respect to dose or formulation are eligible, but patients who have changed to different drugs in the same class are not eligible. Participants taking atazanavir must also be taking ritonavir or a ritonavir-boosted drug to be eligible for this study. More information on this criterion can be found in the protocol.
• Plan to stay on current ART regimen between study screening and Week 24
• AIDS Dementia Scale (ADC) Stage greater than 0
• Cognitive impairment, as evidenced by neuropsychological tests administered at screening
• Progressive neurocognitive decline. More information on this criterion can be found in the protocol.
• Estimated premorbid IQ of 70 or higher indicated by an age-corrected scaled score of 5 or higher on the vocabulary section of the Wechsler Adult Intelligence Scale Revised (WAIS-R) administered at study screening
• Karnofsky performance score of 60 or higher
• Ability to sit and stand for at least 2 hours and swallow medications with an 8-ounce glass of water
• Willing to use acceptable methods of contraception
• Willing to adhere to study schedule

Exclusion Criteria

• Current cancers. Patients with basal cell carcinoma, in situ carcinoma of the cervix, or Kaposi's sarcoma without evidence of visceral involvement or cancer not requiring systemic chemotherapy are not excluded.
• Severe premorbid psychiatric illness, including schizophrenia and major depression, which, in the opinion of the investigator, may interfere with the study
• Active symptomatic AIDS-defining opportunistic infection within 45 days prior to study entry
• Previous or current confounding neurological disorders. More information on this criterion can be found in the protocol.
• Central nervous system infections or cancers. More information on this criterion can be found in the protocol.
• Systemic lupus
• Thyroid disease diagnosed within 24 weeks of study entry
• Active drug or alcohol abuse that, in the opinion of the investigator, may interfere with the study
• Serious illness requiring systemic treatment or hospitalization. Patients who complete therapy or are clinically stable on therapy are not excluded.
• Investigational agents within 45 days prior to study entry. Patients taking expanded access drugs or drugs used in an ACTG protocol for HIV treatment or for HIV-associated complications that are not prohibited by this protocol are not excluded.
• History of allergy/sensitivity to minocycline or other tetracyclines and their formulations
• Any esophageal or other condition that would interfere with a patient's ability to swallow study medication
• Participation in a previous clinical drug research trial of HIV-associated cognitive impairment. Patients who have had an objective decline in performance as defined by the protocol are not excluded.
• Any other clinically significant condition or laboratory abnormality that, in the opinion of the investigator, would interfere with the study
• Certain medications
• Certain abnormal laboratory values. Patients who test positive on nonreactive rapid plasma reagin tests (RPR)are not excluded.
• Inability to undergo lumbar punctures
• Breastfeeding

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

Neurologic AIDS Research Consortium (NARC)

OTHER

Sponsor Role: collaborator

Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ned Sacktor, MD

Role: STUDY_CHAIR

Department of Neurology, Johns Hopkins Bayview Medical Center

Locations

UCLA-David Geffen School of Medicine

Los Angeles, California, United States

University of California

San Diego, California, United States

University of Colorado Health Science Center

Denver, Colorado, United States

The Ponce de Leon Ctr. CRS

Atlanta, Georgia, United States

Northwestern University CRS

Chicago, Illinois, United States

Johns Hopkins School of Medicine

Baltimore, Maryland, United States

Massachusetts General Hospital, Division of Infectious Diseases

Boston, Massachusetts, United States

Henry Ford Hosp. CRS

Detroit, Michigan, United States

Washington University

St Louis, Missouri, United States

NYU Med Ctr, Dept of Medicine

New York, New York, United States

1101 University of Rochester Medical Center, Division of Infectious Diseases

Rochester, New York, United States

University of North Carolina, AIDS Clinical Trials Unit

Chapel Hill, North Carolina, United States

The Research and Education Group - Portland CRS

Portland, Oregon, United States

University of Pennsylvania, ACTU

Philadelphia, Pennsylvania, United States

Virginia Commonwealth Univ. Medical Ctr. CRS

Richmond, Virginia, United States

Univ of Washington, Harborview Medical Ctr

Seattle, Washington, United States

Countries

United States

References

Bell JE. An update on the neuropathology of HIV in the HAART era. Histopathology. 2004 Dec;45(6):549-59. doi: 10.1111/j.1365-2559.2004.02004.x.

Reference Type: BACKGROUND

PMID: 15569045 (View on PubMed)

Ferrari S, Vento S, Monaco S, Cavallaro T, Cainelli F, Rizzuto N, Temesgen Z. Human immunodeficiency virus-associated peripheral neuropathies. Mayo Clin Proc. 2006 Feb;81(2):213-9. doi: 10.4065/81.2.213.

Reference Type: BACKGROUND

PMID: 16471077 (View on PubMed)

Zink MC, Uhrlaub J, DeWitt J, Voelker T, Bullock B, Mankowski J, Tarwater P, Clements J, Barber S. Neuroprotective and anti-human immunodeficiency virus activity of minocycline. JAMA. 2005 Apr 27;293(16):2003-11. doi: 10.1001/jama.293.16.2003.

Reference Type: BACKGROUND

PMID: 15855434 (View on PubMed)

Sacktor N, Miyahara S, Deng L, Evans S, Schifitto G, Cohen BA, Paul R, Robertson K, Jarocki B, Scarsi K, Coombs RW, Zink MC, Nath A, Smith E, Ellis RJ, Singer E, Weihe J, McCarthy S, Hosey L, Clifford DB; ACTG A5235 team. Minocycline treatment for HIV-associated cognitive impairment: results from a randomized trial. Neurology. 2011 Sep 20;77(12):1135-42. doi: 10.1212/WNL.0b013e31822f0412. Epub 2011 Sep 7.

Reference Type: RESULT

PMID: 21900636 (View on PubMed)

Sacktor N, Miyahara S, Evans S, Schifitto G, Cohen B, Haughey N, Drewes JL, Graham D, Zink MC, Anderson C, Nath A, Pardo CA, McCarthy S, Hosey L, Clifford D; ACTG A5235 team. Impact of minocycline on cerebrospinal fluid markers of oxidative stress, neuronal injury, and inflammation in HIV-seropositive individuals with cognitive impairment. J Neurovirol. 2014 Dec;20(6):620-6. doi: 10.1007/s13365-014-0292-0. Epub 2014 Nov 7.

Reference Type: RESULT

PMID: 25377444 (View on PubMed)

Other Identifiers

1U01AI068636

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ACTG A5235

Identifier Type: -

Identifier Source: org_study_id