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

Information source: National Institute of Allergy and Infectious Diseases (NIAID)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: AIDS Dementia Complex; HIV Infections

Intervention: Nimodipine (Drug); Zidovudine (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
Lipton S, Study Chair
Navia B, Study Chair
Simpson D, Study Chair
Tucker T, Study Chair

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.

Clinical Details

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

Study design: Treatment, Double-Blind, Safety Study

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

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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.

Locations and Contacts

UCLA CARE Ctr, Los Angeles, California 90095, United States

Georgetown Univ Med Ctr, Washington, District of Columbia 20007, United States

Northwestern Univ Med School, Chicago, Illinois 60611, United States

Indiana Univ Hosp, Indianapolis, Indiana 462025250, United States

Harvard (Massachusetts Gen Hosp), Boston, Massachusetts 02114, United States

Beth Israel Deaconess Med Ctr, Boston, Massachusetts 02215, United States

Boston Med Ctr, Boston, Massachusetts 02118, United States

Univ of Minnesota, Minneapolis, Minnesota 55455, United States

Univ of Rochester Medical Center, Rochester, New York 14642, United States

Mount Sinai Med Ctr, New York, New York 10029, United States

Columbia Presbyterian Med Ctr, New York, New York 100323784, United States

Univ of North Carolina, Chapel Hill, North Carolina 275997215, United States

Case Western Reserve Univ, Cleveland, Ohio 44106, United States

Julio Arroyo, West Columbia, South Carolina 29169, United States

Univ of Texas Galveston, Galveston, Texas 775550435, United States

Additional Information

Click here for more information about Zidovudine

Related publications:

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.

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)


Last updated: June 23, 2005

Page last updated: June 20, 2008

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