Neurotransmitter - Feb 1995

Clinical Trials

Index
Stroke ALS Parkinson's Disease

Trial of Citicoline in Stroke

A new clinical trail has recently been activated here at the MGH testing the efficacy of citicoline (CDP-choline) in enhancing recovery from stroke. This study is sponsored by Interneuron Pharmaceuticals of Lexington, MA. This project is conducted under the auspices of the MGH Stroke Service, with participation by the staff and fellows of this service. Dr. Seth Finklestein is P.I. and Dr. Ferdinando Buonanno is an investigator of the study here at the MGH and Dr. Jill Kaplan is the PI of this study at the Spaulding Rehab Hospital. This study is an example of several collaborative studies on neurorecovery after stroke that we hope to initiate jointly with the SRH. In particular, we are now beginning "functional MR" studies of mechanisms of brain plasticity and recovery following stroke. Citicoline is a substrate for phosphatidylcholine, a constituent of the neural membrane. When an excess of CDP-choline is ingested orally, it enters the blood brain barrier, and increase phosphatidylcholine synthesis in brain. Since re-establishment of the integrity of the neuronal membrane may be an important aspect of recovery from stroke or head injury, it is conceivable that this compound might accelerate such recovery. Indeed, in several animal models, and in clinical trials both in Europe and Japan, there is a suggestion that this compound, indeed, enhances recovery from stoke or head injury. An important aspect of this compound is that it is very well tolerated when taken orally, and seems to be without major side effects.

We are seeing your assistance in identifying patients within 24 hours of the onset of stroke. Such patients agreeing to participate in this study will be randomized to receive placebo or citicoline, and will be evaluated by a full battery of neurological and neuropsychological tests for the next 12 weeks. To my knowledge this is one of the first studies to test a compound that might enhance functional recovery after completed stroke.

When such patients with stroke in the first 24 hours are identified, we would ask you to page Dr. Ufuk Can 726-2241 or 726-2066 (beeper #1214) of the Stroke Service as soon as possible. Dr. Can will then determine the formal eligibility of the patient for the study, and having determined this, we will seek informed consent for participation.

Seth Finklestein, M.D.

Anti-Oxidant Therapy in ALS

The Neuromuscular Unit is still actively recruiting patients with amyotrophic lateral sclerosis for a one year placebo controlled double-blind clinical trial evaluating the efficacy of anti-oxidant therapy. The inclusion criteria are patients with clinically diagnosed ALS who are ambulatory. We are seeking a total of 40 patients. Please contact either Dr. Didier Cros (726-3642) or Dr. Merit Cudkowicz (724-1873) with questions and patient referrals.

Merit Cudkowicz

Movement Disorders Trial

The Movement Disorders Unit is now actively recruiting Parkinson's disease (PD) patients with levo-dopa exacerbated psychosis for a clinical trial comparing two treatments; Risperidone and Clozapine.

The clinical study will test the hypothesis that Risperidone, a new anti-psychotic drug, is as effective as Clozapine in treatment of levodopa-exacerbated psychosis in Parkinson's disease (PD) patients. In addition, quantitative electrophysiologic methods will be applied to test the hypothesis that Risperidone and/or Clozapine improves tremor and rigidity in PD patients with psychosis.

Both Risperidone and Clozapine are currently used to treat symptoms of psychosis, including hallucinations and delusions. The advantage in PD patients of both Risperidone and Clozapine, compared with conventional anti-psychotic agents, is the marked lower risk of extrapyramidal motor side effects. In several small clinical studies, Clozapine therapy successfully improved psychosis in PD patients without worsening extrapyramidal symptoms. Preliminary observations suggest that Clozapine may also improve tremor and dyskinesia in PD. Clozapine therapy is associated with sedation, hypotension, salivation and a 1 % risk of agranulocytosis which requires weekly blood counts for the duration of therapy. Because of these side effects, efforts have been made to find another drug which will improve the symptoms of psychosis in patients with Parkinson's disease. Risperidone, lacks the hematologic and systemic side effects associated with Clozapine therapy and may be as effective as Clozapine in the treatment of psychosis in PD. Risperidone has not been as extensively tested in PD as Clozapine, but should Risperidone prove to be as effective as Clozapine in the treatment of psychosis in PD, it will be an easier and safer drug to use for this indication.

For these reasons, we are conducting a randomized, double blind clinical trial comparing the efficacy of Risperidone with that of Clozapine in the treatment of psychosis in patient's with Parkinson's disease. We expect to enroll twenty patients. Each patient will receive treatment for 3 months.

The investigators are Drs. Merit Cudkowicz and John H. Growdon, and Mrs. Terry Ellis. For questions or patient referrels, please contact either Dr. Cudkowicz at 617-724-1873 or Dr. Growdon at 617-726-1728.

Merit E. Cudkowicz

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John Lester (lester@helix.mgh.harvard.edu).