A phase I/II trial of nimodipine for HIV-related neurologic complications

Bradford A. Navia, U. Dafni, D. Simpson, T. Tucker, E. Singer, J. C. McArthur, Constantin Yiannoutsos, L. Zaborski, S. A. Lipton

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Background: Few effective treatments are available for AIDS dementia complex (ADC) and HIV-associated neuropathy. However, recent in vitro studies indicate that nimodipine, a voltage-dependent calcium channel antagonist, can prevent HIV-related neuronal injury and may provide a novel form of treatment for these disorders. Methods: To determine the safety and possible efficacy of this agent, 41 patients with mild to severe ADC, including 19 patients with neuropathy, were entered into the AIDS Clinical Trial Group multicenter, phase-I and phase-II study. Nimodipine at 60 mg po, five times daily; 30 mg po, three times daily; or placebo was administered for 16 weeks as adjuvant treatment to antiretroviral therapy. Results: Neuropsychological performance at baseline, measured by the composite neuropsychological Z score (NPZ-8), correlated significantly with the ADC stage and with CSF levels of neopterin, a marker of immune activation. No significant differences in toxicity were observed among the three arms. Intent-to-treat analysis showed no significant change in the NPZ-8, although improvement was suggested in the high-dose arm. In addition, a trend toward stabilization in peripheral neuropathy was observed in both nimodipine arms compared with placebo. Conclusions: Nimodipine and other similar nonantiretroviral agents may provide a safe and promising avenue of treatment for neurologic disorders associated with HIV infection. The results of this study indicate that further clinical trials are warranted.

Original languageEnglish (US)
Pages (from-to)221-228
Number of pages8
JournalNeurology
Volume51
Issue number1
StatePublished - Jul 1998
Externally publishedYes

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Nimodipine
Nervous System
AIDS Dementia Complex
HIV
Placebos
Clinical Trials
Neopterin
Therapeutics
Calcium Channel Blockers
Proxy
Peripheral Nervous System Diseases
Calcium Channels
Nervous System Diseases
HIV Infections
Acquired Immunodeficiency Syndrome
Biomarkers
Safety
Wounds and Injuries

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Navia, B. A., Dafni, U., Simpson, D., Tucker, T., Singer, E., McArthur, J. C., ... Lipton, S. A. (1998). A phase I/II trial of nimodipine for HIV-related neurologic complications. Neurology, 51(1), 221-228.

A phase I/II trial of nimodipine for HIV-related neurologic complications. / Navia, Bradford A.; Dafni, U.; Simpson, D.; Tucker, T.; Singer, E.; McArthur, J. C.; Yiannoutsos, Constantin; Zaborski, L.; Lipton, S. A.

In: Neurology, Vol. 51, No. 1, 07.1998, p. 221-228.

Research output: Contribution to journalArticle

Navia, BA, Dafni, U, Simpson, D, Tucker, T, Singer, E, McArthur, JC, Yiannoutsos, C, Zaborski, L & Lipton, SA 1998, 'A phase I/II trial of nimodipine for HIV-related neurologic complications', Neurology, vol. 51, no. 1, pp. 221-228.
Navia BA, Dafni U, Simpson D, Tucker T, Singer E, McArthur JC et al. A phase I/II trial of nimodipine for HIV-related neurologic complications. Neurology. 1998 Jul;51(1):221-228.
Navia, Bradford A. ; Dafni, U. ; Simpson, D. ; Tucker, T. ; Singer, E. ; McArthur, J. C. ; Yiannoutsos, Constantin ; Zaborski, L. ; Lipton, S. A. / A phase I/II trial of nimodipine for HIV-related neurologic complications. In: Neurology. 1998 ; Vol. 51, No. 1. pp. 221-228.
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