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

Primary Purpose

AIDS Dementia Complex, HIV Infections

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Nimodipine
Zidovudine
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for AIDS Dementia Complex focused on measuring Central Nervous System Diseases, Acquired Immunodeficiency Syndrome, AIDS Dementia Complex, AIDS-Related Complex, Zidovudine, Nimodipine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • UCLA CARE Center CRS
  • Northwestern University CRS
  • Indiana Univ. School of Medicine, Infectious Disease Research Clinic
  • Massachusetts General Hospital ACTG CRS
  • Bmc Actg Crs
  • Beth Israel Deaconess - East Campus A0102 CRS
  • University of Minnesota, ACTU
  • Washington U CRS
  • Univ. of Rochester ACTG CRS
  • Unc Aids Crs
  • Case CRS
  • University of Washington AIDS CRS

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 27, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Miles, Glaxo Wellcome
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1. Study Identification

Unique Protocol Identification Number
NCT00000738
Brief Title
Randomized, Double-Blind, Placebo-Controlled Trial of Nimodipine for the Neurological Manifestations of HIV-1
Official Title
Randomized, Double-Blind, Placebo-Controlled Trial of Nimodipine for the Neurological Manifestations of HIV-1
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
June 1994 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Miles, Glaxo Wellcome

4. Oversight

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
AIDS Dementia Complex, HIV Infections
Keywords
Central Nervous System Diseases, Acquired Immunodeficiency Syndrome, AIDS Dementia Complex, AIDS-Related Complex, Zidovudine, Nimodipine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Masking
Double
Enrollment
36 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Nimodipine
Intervention Type
Drug
Intervention Name(s)
Zidovudine

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lipton S
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Navia B
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Simpson D
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Tucker T
Official's Role
Study Chair
Facility Information:
Facility Name
UCLA CARE Center CRS
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Northwestern University CRS
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Massachusetts General Hospital ACTG CRS
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Bmc Actg Crs
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Beth Israel Deaconess - East Campus A0102 CRS
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Minnesota, ACTU
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Washington U CRS
City
Saint Louis
State/Province
Missouri
Country
United States
Facility Name
Univ. of Rochester ACTG CRS
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Unc Aids Crs
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Case CRS
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
University of Washington AIDS CRS
City
Seattle
State/Province
Washington
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
9674806
Citation
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.
Results Reference
background
Citation
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)
Results Reference
background

Learn more about this trial

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

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