• Berk, Steve S (PI)

Project: Research project

Project Details


This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. To determine whether the pharmacokinetics of methadone are affected by coadministration of Peginterferon alfa -2b. RESEARCH DESIGN AND METHODS a. Medical: Prior to study entry, an outpatient evaluation will be completed on all candidates who appear to meet admission criteria after an initial screening. This evaluation will include a physical examination and the following laboratory studies: CBC (including WBC, differential, hemoglobin, hematocrit, platelet count), creatinine, urinalysis, liver function tests (SGOT, SGPT, LDH, alkaline phosphatase, total and direct bilirubin), HIV viral load, CD4 count, and a quantitative HCV RNA will be measured. Urine will be tested for recent use of, cocaine, marijuana, opiates, amphetamines, and benzodiazepines and an alcohol breathalyzer test will be performed . If patients are admitted to the study they will be evaluated clinically at designated intervals (see Table 1 below). b. Psychiatric/Behavioral: To ensure that subjects meet the study diagnostic criteria prior to admission, a semistructured outpatient screening interview will be conducted. Assessment instruments will include: (1) the MINI International Neuropsychiatric Interview (M.I.N.I.)\super 2\nosupersub and (2) Addiction Severity Index-Lite (ASI-Lite), an instrument which employs both objective and subjective information as a measure of severity of substance use and substance-related problems across 7 domains (drug use, alcohol use, family/social, medical, psychiatric, legal, and employment). In addition, the Subjective Opiate Withdrawal Scale (SOWS)\ and the Objective Opiate Withdrawal Scale (OOWS) (a set of 29-item self and observer rating scales developed for use in opiate pharmacotherapy treatment clinics which elicits information about opiate withdrawal and medication side effects in the past week) will be administered to all study participants. We will also use the Beck Depression Inventory (BDI) to monitor for depression during the study. This is a commonly used self administered questionnaire consisting of 21 items, each with four statements arranged in increasing severity about a particular symptom of depression. Again, if patients are admitted to the study they will be evaluated as above at designated intervals (see Table 1 below). c. Biochemical: All clinical chemistries, CBC, HCV RNA and serum levels of methadone will be measured by the Department of Laboratory Services at Montefiore Medical Center according to standard procedure. HIV viral loads and CD counts will be measured through the above mentioned Basic Science CFAR Cores. Specific Study Procedures Subjects who are opioid dependent and on a stable (for at least 8 weeks) daily dose of 40 - 200mg of methadone will be eligible to participate in these studies. Upon enrollment, a urine toxicology screen will be obtained to document whether other illicit substances have been recently ingested. An alcohol breathalyzer test must also be negative for the study to proceed. Subjects will receive their usual methadone dose by 9 am in the morning daily. Methadone administration will be observed at least five days/week during the study period. On day 3, subjects will be admitted to the GCRC for their first of two 24-hour pharmacokinetic studies. They will receive their morning methadone dose at the GCRC. Plasma methadone pharmacokinetics will be determined by measuring 8 strategically timed serial methadone concentrations over a 24 hour period (at 0, 1, 2, 4, 6, 8, 12 and 24 hours). On day 4, subjects will begin weekly subcutaneous administration of Peginterferon alfa -2b at a dose of 1.5 mcg/kg (rounded off to the nearest practical increment as recommended in Peg-Intron manufacturer's prescribing recommendations) for 2 weeks. Thus, the dose of Peginterferon will be given on study day 11. On study day 18 (one week after the second Peginterferon dose), subjects will undergo a second methadone pharmacokinetic study. After completing the second 24 hour pharmacokinetic study, subjects who wish to receive a full course of HCV treatment will continue weekly Peginterferon and start ribavirin at the usual recommended oral daily dose as prescribed by their primary physician and/or gastroenterologist. For those who do not wish to be treated for HCV no further interferon will be administered. Data Analysis/Statistics\b0 Pharmacokinetics analysis of the methadone plasma levels will include determination of the area under the concentration-time curve (AUC), maximum and minimum concentration, half-life, and oral clearance and volume of distribution alone and after Peginterferon administration. Pharmacokinetic variables will be compared using a 2-tailed t-test. A sample size of 16 was chosen to achieve 80% power with a 0.05 significance level to detect a 25% change in a parameter after Peginterferon, when the expected difference is zero and the coefficient of variation of the difference is 33%.
Effective start/end date12/1/0511/30/06


  • National Center for Research Resources: $43,462.00


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    Spiegel, A. M., Purpura, D., Spiegel, A. A. M., Howard, A. A. A., Melman, A. A., Bloom, B. B. R., Diamond, B. B., Segal-isaacson, C. C., Stein, D. D. C., Purpura, D. D., Schoenbaum, E., Kaskel, F. F., Ho, G. G. Y., Shamoon, H., Hetherington, H. H. P., Crystal, H. H., Roy-chowdhury, J. J., Pollard, J. J. W., Rieder, J. J., Crandall, J. J. P., Wylie-Rosett, J., Pan, J. J. W., Rossetti, L. L., Weiss, L. M., Bigal, M. M., Hawkins, M. A., Brownlee, M. M. A., Alderman, M. M. H., Schilsky, M. M. L., Fabry, M. M. E., Roy-chowdhury, N. N., Barzilai, N. N. J., Fleischer, N. N. S., Santoro, N. N. F., Kennan, R. R. P., Bookchin, R. R. M., Klein, R. R. M., Lipton, R. B., Burk, R. R. D., Nagel, R. R. L., Engel, S. S. S., Gupta, S. S., Somlo, S. S., Berk, S. S., Weber, T. T. J., Frishman, W. W. H., Noyer, C. C., Barzilai, N., Burk, R. D., Fabry, M. E., Fleischer, N., Hawkins, M. A., Ho, G. Y., Kaufman, H. L., Nagel, R. L., Roy-Chowdhury, J., Rubenstein, A., Santoro, N. F., Schilsky, M. L., Shamoon, H., Somlo, S., Stein, D. T., Wadler, S. H., Wozniak, R. & Wylie-Rosett, J.

    National Center for Research Resources


    Project: Research project