Cognitive impairment is a common and disabling complication of advanced HIV infection. Antiretroviral agents are the only proven therapies currently used for the treatment of HIV dementia, but the response to these agents is frequently unsatisfactory, short-lived or complicated by intolerable side effects. We hypothesized that OPC-14, 117, a lipophilic antioxidant similar to Vitamin E which acts to scavenge superoxide anion radicals, might interfere with toxic interactions between HIV infected macrophages and neurons. We conducted a double- blind, placebo-controlled randomized clinical trial to assess the safety and tolerability of OPD C-14,117 240 mg. per day. Informed, witnessed, signed consent was obtained from all participants or from persons with durable power of attorney. All 7 patients at our site had cognitive impairment according to performance on neuropsychological tests. The double-blind, placebo-controlled phase of the study was 12 weeks. After this phase, patients were eligible to receive 12 weeks of open label drug. Evaluations included neurological and neuropsychological assessments, concurrent medications, concurrent AIDS-defining illnesses, adverse experiences, activities of daily living assessment and routine safely labs. The primary outcome measure was tolerability: the proportion of subjects able to complete the study on their assigned dosage of experimental medication. Overall OPC-14,117 was as well tolerated as placebo. There were three early terminations, none due to study medication. There were trends toward improvement in the cognitive test scores, however, these were not statistically significant. These results demonstrate that this antioxidant intervention is well tolerated in cognitively impaired patients with advance HIV infection, and suggest that a larger efficacy trial to assess the impact of OPC-14,117 on cognitive performance is warranted. The trial was completed as of January 10, 1996.
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