Poster Abstracts: 1-6
ASENT 4th Annual Meeting
Thursday, March 14 - Saturday, March 16, 2002
Capital Hilton Hotel Washington, DC
Poster Abstracts: 1-6
ATTITUDES TOWARDS EMERGENCY RESEARCH CONSENT WAIVER AT A LEVEL 1 TRAUMA EMERGENCY CENTER
C. Contant 1, L. Mangus 2, C. Robertson 1, A. Valadka 1, B. Brody 2, 1Department of Neurosurgery and the 2Center for Medical Ethics and Health Policy, Baylor College of Medicine, Houston, Texas 77030 USA
The NIH has provided procedures for conduct of research under an Emergency Research Consent Waiver (ERCW). Under this rule, consultation with the "at risk" community is required. A questionnaire was given to a gender and ethnicity stratified sample of 480 individuals in the Waiting Room of the Emergency Center of the Level 1 Trauma Center at Ben Taub General Hospital in Houston, Texas. A description of an on-going study in patients with sever brain trauma being conducted at Ben Taub was given. Participants were then asked five primary questions, followed by several demographic questions. The primary items assessed attitudes towards the relative risks/benefits of the study, the use of randomization and ERCW, conduct of the study in a public hospital and whether the respondent would wish to be enrolled in the study, if needed. Each item was asked in a "positive" or "negative" manner. Log-linear models were fit to examine the effects of gender, ethnicity and the manner of asking the question for the primary items. Relatively few interactions among these factors were found. A high proportion of the respondents (86.6%) were willing to enroll themselves or a family member in the study if needed. Use of randomization and waiver received less positive approval (53% and 59% respectively). The overall high personal acceptance of the clinical study was tempered by some concern over the policy of randomization and waiver. Emergency room waiting area surveys may provide an in-depth understanding of the attitudes of the population at risk for ERCW.
Supported by NINDS.
EXPERIENCE WITH NEW ENTERIC-COATED WEEKLY FLUOXETINE
S. Levy, Philadelphia College of Osteopathic Medicine, Westchester, PA 19380; J.M. Plewes, M.G. Wilson, Eli Lilly and Company, Indianapolis, IN 46285
A new formulation enteric-coated fluoxetine given once weekly has been shown in clinical trials to be well tolerated, effective and associated with greater compliance. However, there have been few literature reports on its use in naturalistic clinical sitting. Seventy-one psychiatric outpatients with a confirmed diagnosis of clinical depression from our clinic participated. They were stable, in complete remission and had been compliant on their daily fluoxetine for an average of 3.1 years. Four patients began weekly dosing as a part of their acute therapy. We extracted data from patient charts, and we collected a quantitative evaluation of the severity of their depression. All patients were successfully converted from a single daily dose to a single weekly dose. All patients including the four acute therapy patients are presently in remission. This cohort has been monitored and has a cumulative exposure of 32.1 patient-years. A statistically significant average improvement of 21.0 points, with a standard error of 1.8, from beginning of acute therapy to follow-up on weekly dosing on the modified Zung was observed (p-value < 0.001). No serious adverse events or hospitalizations were reported for any patient. In our community-based outpatient psychiatric clinic, we see patients with substantial medical and psychiatric comorbid disorders. In a subgroup of this population, we observed that weekly doses of enteric-coated fluoxetine were tolerable and effective for long-term continuation treatment of major depressive disorder. The simple, once weekly, higher dosing offers a convenient alternative for some patients during long-term treatment of depression.
Funding provided by Eli Lilly and Company
ALZHEIMERS DISEASE (AD) PATIENTS’ AND CAREGIVERS’ CAPACITY, COMPETENCY, AND REASONS TO ENROLL IN AN EARLY PHASE AD CLINICAL TRIAL.
J.H.T Karlawish, D.J. Casarett, B.D. James, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104
To examine AD patients’ and caregivers’ (CG’s) capacity, competency and reasons for enrolling in an early phase AD clinical trial, interviews were conducted with 15 mild-moderate AD patients, 15 age and education matched nondemented elderly persons, and 15 CG’s. Capacity was measured using the MacArthur Competency Assessment Tool for Clinical Research, competency was judged by a study coordinator who reviewed tape recordings of the capacity interviews, and the reasons for a decision were determined by coding of the capacity interviews. On all measures except the ability to make a choice, patients performed worse than controls (understanding p=0.001; appreciation p=0.005; reasoning p=0.0005), and CG’s (understanding p=0.0002; appreciation p=0.003; reasoning p=0.0003). Using the controls’ performance to set psychometric criteria to define capacity, the proportions of patients with adequate understanding, appreciation and reasoning were: 6/15 (40%), 3/15 (20%) and 5/15 (33%). All CG’s and 8/15 (53%) patients were competent. Reasons for enrolling typically featured the potential benefit to the patients’ health or well-being, and altruism expressed either as a desire to help other patients or family, or a desire to contribute to scientific knowledge. The MacCAT-CR is a reliable and valid way to assess patient capacity and competency to enroll in an early phase clinical trial. While many patients have significant impairments in their capacity, some mild stage patients are competent. Reasons to enroll in an early phase trial blend an expectation of therapeutic benefit and a desire to help others.
NEOTROFINTM IS NEUROPROTECTIVE IN AN ANIMAL MODEL OF PARKINSON’S DISEASE
F.J. Huff, N. Hauptmann, M.Yan, and D.R. Helton, Discovery Research, NeoTherapeutics, Irvine, CA, USA
NeotrofinTM (AIT-082) has been shown to improve memory in both animals and humans. In animal models, Neotrofin has been demonstrated to have neuroprotective and neuroregenerative properties. Currently, Neotrofin is in late stage clinical trials for the treatment of Alzheimer’s disease. The purpose of this study was to determine if Neotrofin would exhibit neuroprotective activity in a model of Parkinson’s disease in the rat. Circling behavior and altered dopamine metabolism were evaluated in unilaterally 6-OHDA-lesioned rats. Rats were administered Neotrofin or vehicle 15 minutes before lesioning of the substantia nigra and Day 1 and daily thereafter for 30 days. Apomorphine administration and behavioral monitoring was performed every third day beginning on Day 15. Neotrofin (10 mg/kg, s.c.) reduced the rotations induced by apomorphine relative to controls. In addition to the decrease in response magnitude, the onset of the rotations produced by apomorphine was delayed in rats treated with Neotrofin. These results indicate that Neotrofin partially protects nigrostriatal dopaminergic neurons from the neurodegeneration produced by the toxin 6-OHDA. These results extend previous data showing that Neotrofin is neuroprotective and support its use as a potential therapy of Parkinson’s disease. A phase IIA clinical study of Neotrofin in patients with early stage Parkinson’s disease is currently ongoing.
THE DEVELOPMENT OF A NOVEL SERIES OF COMPOUNDS FOR THE TREATMENT OF PSYCHOSIS AND MOOD-RELATED DISORDER
D. Helton, E. Pfadenhauer, P. Mohan, and E. Taylor. Discovery Research, NeoTherapeutics, Irvine, CA, USA
We have synthesized a series of antipsychotic compounds. These novel compounds have been designed to have cognitive enhancing properties and a restricted receptor profile, thus targeting the basic symptoms of schizophrenia and intractable symptoms of schizophrenia (i.e. cognitive impairment), while minimizing secondary pharmacology commonly associated with antipsychotics. We characterized the behavioral, neurochemical, biochemical, and toxicological activity of select compounds. As examples of the series, NEO-356 and NEO-377 have selective dopaminergic and serotinergic receptor binding activity and little to no adrenergic, histaminergic or muscarinic receptor binding. Both compounds reverse PCP-induced disruption of pre-pulse inhibition indicating that they may have clinical utility in the treatment of psychosis. NEO-377 also disrupts conditioned avoidance responding (CAR) indicating that like other atypical antipsychotics, it may disrupt cognition. However, NEO-356 does not disrupt CAR and may therefore represent a structural class that enhances cognition. NEO-356 attenuates PCP-and not MK-801-induced hyper-locomotion, whereas NEO-377 attenuates MK-801-and not PCP-induced hyper-locomotion. These two examples highlight the functional diversity of the series. The characterization of several compounds in comparison to clozapine and risperidone will be represented.
DELUSIONS IN AD ARE LINKED TO DEMENTIA SEVERITY, ESPECIALLY FRONTAL-LOBE IMPAIRMENTS
C. Walulik, J. Locascio, M. Korczykowski, and J.H. Growdon, Massachusetts General Hospital, Boston, MA 02114
The purpose of this study was to determine if behavioral disturbances in probable AD patients correlate with either global estimates of dementia severity or specific cognitive impairments. 64 probable AD patients completed a set of 4 examinations within 3 months: the information-memory-concentration subscale of the Blessed Dementia Scale (BDS) and a set of formal cognitive tests were administered to each patient, and the Activities of Daily Living questionnaire (ADL) and the Neuropsychiatric Inventory (NPI) were completed by the caregiver. The data were analyzed by Pearson correlation coefficients. Analyses from the NPI were limited to these domains: depression, delusions, and hallucinations. Of these three, only delusional frequency (p<0.002) and severity (p<0.0007) correlated with extent of dementia severity. Within the set of cognitive tests, delusions correlated with deficits on frontal-lobe tests such as the Stroop test (p<0.02) and verbal fluency for letters (p<0.03). Overall, these findings reinforce the association between delusions and frontal lobe dysfunction in AD.
This project was funded by the Alzheimer’s Disease Research Center at the Massachusetts General Hospital (P50 AG05134).