Randomized, Double-Blind, Placebo-Controlled Trial of Nimodipine for the Neurological Manifestations of HIV-1

NCT00000738 | Completed Phase 1

• 2 other identifiers: ACTG 16211137
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 12

Brief Summary

PRIMARY: To assess the safety of nimodipine in the treatment of HIV-Associated Motor / Cognitive Complex (formerly AIDS dementia complex). To assess the systemic or central nervous system toxicities (e.g., rash, headache, gastrointestinal symptoms, nausea, dyspnea, muscle pain or cramp, acne) of nimodipine. SECONDARY: To assess the efficacy of nimodipine in stabilizing the progression of HIV-Associated Motor / Cognitive Complex by improvement in neuropsychological test performance, peripheral neuropathy, or other neurologic manifestations. HIV-infected patients may develop a condition known as HIV-Associated Motor / Cognitive Complex (also known as AIDS dementia complex) that causes damage to the nervous system, particularly the brain and spinal cord. Evidence exists that nimodipine protects nerve cells in culture from injury by HIV. Although nimodipine has been used in patients with other neurological problems, its safety and effectiveness in halting the progression of HIV-Associated Motor / Cognitive Complex is not yet known.

Conditions

AIDS Dementia Complex; HIV Infections

Keywords

Central Nervous System Diseases; Acquired Immunodeficiency Syndrome; AIDS Dementia Complex; AIDS-Related Complex; Zidovudine; Nimodipine

Interventions

Nimodipine DRUG

Zidovudine DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Concurrent Medication:
• Allowed:
• Alternative or additional antiretroviral agents if on a stable dose for 8 weeks prior to study entry.
• Isoniazid.
• Anticonvulsants.
• Benzodiazepines and antidepressants (provided dose is stable prior to study entry).
• Symptomatic therapies (e.g., analgesics, antihistamines, antiemetics, and antidiarrheal agents).
• Maintenance therapy with clarithromycin, azithromycin, amikacin, ethambutol, clofazimine, ciprofloxacin, and rifampin for disseminated Mycobacterium avium infection.
• Maintenance therapy for opportunistic infections (e.g., PCP, MAI, CMV).
• Patients must have:
• Documented HIV infection.
• HIV-Associated Motor / Cognitive Complex.
• Acceptable neurological and neuropsychological impairment scores.
• Estimated premorbid IQ of 70 or greater, consistent with completion of the sixth grade or ability to read at the sixth grade level. Current ability to read and comprehend a newspaper or history of such ability will satisfy this criterion for patients whose formal education stopped before the sixth grade. For patients who are illiterate, ability to make change from a dollar for a combined purchase of two items or the history of such ability will satisfy this criterion. In the absence of a functional definition, an age-correlated scaled score of \> 5 on the Vocabulary Subtest of the WAIS-R or WISC-R may be used to establish IQ.
• Ability to provide written informed consent.

You may not qualify if:

• Co-existing Condition:
• Patients with the following symptoms and conditions are excluded:
• Active symptomatic AIDS-defining opportunistic infection (maintenance therapy for opportunistic infections, e.g., Pneumocystis carinii pneumonia, Mycobacterium avium infection, and cytomegalovirus, is permitted).
• Neoplasms other than basal cell carcinoma, in situ carcinoma of the cervix, or Kaposi's sarcoma without evidence of visceral involvement or that do not require systemic chemotherapy.
• Confounding neurological disorders, including the following:
• a) neurologic disease unrelated to HIV infection (such as multiple sclerosis, documented stroke, degenerative disease); b) chronic seizure disorders or head injuries if the condition results in functional impairment or is likely to interfere with evaluations; c) central nervous system (CNS) infections or neoplasms (such as toxoplasmosis, primary or metastatic CNS lymphoma, progressive multifocal leukoencephalopathy, cryptococcal or other fungal meningitis, tuberculous CNS infections, or untreated neurosyphilis).
• Severe premorbid psychiatric illness including bipolar illness, schizophrenia, and depression requiring electroconvulsive therapy.
• Major depression likely to interfere with evaluation or protocol compliance.
• Concurrent Medication:
• Excluded:
• Major psychotropic medication, including MAO inhibitors, phenothiazines, butyrophenones, barbiturates, or amphetamines (unless a stable dose is maintained for 30 days prior to study entry).
• Any ongoing maintenance therapy for confounding neurological disorders.
• Patients with the following prior conditions are excluded:
• Prior Medication:
• Excluded:

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Miles: collaborator
• Glaxo Wellcome: collaborator

Study Sites (12)

UCLA CARE Center CRS

Los Angeles, California, 90095, United States

Location

Northwestern University CRS

Chicago, Illinois, 60611, United States

Location

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

Indianapolis, Indiana, 46202, United States

Location

Massachusetts General Hospital ACTG CRS

Boston, Massachusetts, 02114, United States

Location

Bmc Actg Crs

Boston, Massachusetts, 02118, United States

Location

Beth Israel Deaconess - East Campus A0102 CRS

Boston, Massachusetts, 02215, United States

Location

University of Minnesota, ACTU

Minneapolis, Minnesota, 55455, United States

Location

Washington U CRS

St Louis, Missouri, United States

Location

Univ. of Rochester ACTG CRS

Rochester, New York, 14642, United States

Location

Unc Aids Crs

Chapel Hill, North Carolina, 27599, United States

Location

Case CRS

Cleveland, Ohio, 44106, United States

Location

University of Washington AIDS CRS

Seattle, Washington, United States

Location

Related Publications (2)

• Navia BA, Dafni U, Simpson D, Tucker T, Singer E, McArthur JC, Yiannoutsos C, Zaborski L, Lipton SA. A phase I/II trial of nimodipine for HIV-related neurologic complications. Neurology. 1998 Jul;51(1):221-8. doi: 10.1212/wnl.51.1.221.

  PMID: 9674806 BACKGROUND

• Galgani S, Narciso P, Balestra P, Pigorini F, Pau F, Sette P, Tozzi V, Alba L, Grisetti S, Visco G. Nimodipine+ZDV vs ZDV in patients with ADC. Int Conf AIDS. 1994 Aug 7-12;10(1):205 (abstract no PB0248)

  BACKGROUND

MeSH Terms

Conditions

AIDS Dementia Complex; HIV Infections; Central Nervous System Diseases; Acquired Immunodeficiency Syndrome; AIDS-Related Complex

Interventions

Nimodipine; Zidovudine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Dementia; Brain Diseases; Nervous System Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Neurocognitive Disorders; Mental Disorders; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nicotinic Acids; Thymidine; Pyrimidine Nucleosides; Pyrimidines; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Lipton S

  STUDY CHAIR

• Navia B

  STUDY CHAIR

• Simpson D

  STUDY CHAIR

• Tucker T

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: DOUBLE
• Purpose: TREATMENT
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: August 31, 2001
• Study Completion: June 1, 1994
• Last Updated: November 4, 2021

Record last verified: 2021-10

Locations

US (12)