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

This study has been completed.
Sponsor:
Collaborators:
Miles
Glaxo Wellcome
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000738
First received: November 2, 1999
Last updated: March 30, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
AIDS Dementia Complex
HIV Infections
Drug: Nimodipine
Drug: Zidovudine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Randomized, Double-Blind, Placebo-Controlled Trial of Nimodipine for the Neurological Manifestations of HIV-1

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 36
Study Completion Date: June 1994
Detailed Description:

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.

Forty patients currently taking zidovudine (AZT) or any other approved antiretroviral agent will be randomized to one of three treatment arms: high-dose nimodipine, low-dose nimodipine, or placebo. Additionally, six patients who are intolerant to standard antiretroviral therapy will be randomized to receive high- or low-dose nimodipine. Nimodipine is administered by mouth concurrently with patients' prestudy dose of antiretroviral agent. Treatment is given for 16 weeks, and patients are followed every 4 weeks. As an option, all patients may receive an additional 16 weeks of low-dose nimodipine.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

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.

Prior Medication:

Required:

  • AZT for at least 12 weeks prior to study entry or any other approved antiretroviral agent (i.e., ddI or ddC) for at least 8 weeks prior to study entry, except in antiretroviral-intolerant patients who must be off antiretrovirals for at least 4 weeks.

Exclusion Criteria

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:

Confounding neurological disorders defined in the "Exclusion Co-existing Conditions" field.

Prior Medication:

Excluded:

  • Investigative drugs within 30 days prior to study entry.
  • Confounding calcium channel antagonists (such as nifedipine, verapamil, diltiazem, and related drugs) within 4 weeks prior to study entry.

Active alcohol or drug abuse.

  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: NCT00000738

Locations
United States, California
UCLA CARE Center CRS
Los Angeles, California, United States, 90095
United States, Illinois
Northwestern University CRS
Chicago, Illinois, United States, 60611
United States, Indiana
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Massachusetts General Hospital ACTG CRS
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess - East Campus A0102 CRS
Boston, Massachusetts, United States, 02215
Bmc Actg Crs
Boston, Massachusetts, United States, 02118
United States, Minnesota
University of Minnesota, ACTU
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Washington U CRS
St. Louis, Missouri, United States
United States, New York
Univ. of Rochester ACTG CRS
Rochester, New York, United States, 14642
United States, North Carolina
Unc Aids Crs
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Case CRS
Cleveland, Ohio, United States, 44106
United States, Washington
University of Washington AIDS CRS
Seattle, Washington, United States
Sponsors and Collaborators
Miles
Glaxo Wellcome
Investigators
Study Chair: Lipton S
Study Chair: Navia B
Study Chair: Simpson D
Study Chair: Tucker T
  More Information

Additional Information:
Publications:
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)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000738     History of Changes
Other Study ID Numbers: ACTG 162, 11137
Study First Received: November 2, 1999
Last Updated: March 30, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Central Nervous System Diseases
Acquired Immunodeficiency Syndrome
AIDS Dementia Complex
AIDS-Related Complex
Zidovudine
Nimodipine

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
AIDS Dementia Complex
Dementia
Neurologic Manifestations
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Signs and Symptoms
Nimodipine
Zidovudine
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents

ClinicalTrials.gov processed this record on July 22, 2014