Rosiglitazone for Clozapine Induced Glucose Metabolism Impairment

Summary

We propose an eight-week, double-blind, placebo-controlled trial of rosiglitazone in schizophrenia subjects treated with clozapine using Bergman's Minimal Model (MINMOD) intravenous glucose tolerance test. Bergman's Minimal Model analysis with frequent sampled intravenous glucose tolerance test (FSIVGTT) provides a sensitive and reliable method to measure glucose effectiveness, insulin secretion and insulin sensitivity. The MINMOD determines the relationship between insulin sensitivity, insulin secretion and the degree of obesity and can be used to study drug effects upon these variables.

Timeline

Start

2003-09

Primary completion

2011-01

Completion

2011-01

Publications

• Background AMDISEN A. DRUG-PRODUCED OBESITY. EXPERIENCES WITH CHLORPROMAZINE, PERPHENAZINE AND CLOPENTHIXOL. Dan Med Bull. 1964 Oct;11:182-9. No abstract available.
• Background Bergman RN. Lilly lecture 1989. Toward physiological understanding of glucose tolerance. Minimal-model approach. Diabetes. 1989 Dec;38(12):1512-27. doi: 10.2337/diab.38.12.1512.
• Background Cohen S, Chiles J, MacNaughton A. Weight gain associated with clozapine. Am J Psychiatry. 1990 Apr;147(4):503-4. doi: 10.1176/ajp.147.4.503.
• Background Cosway R, Strachan MW, Dougall A, Frier BM, Deary IJ. Cognitive function and information processing in type 2 diabetes. Diabet Med. 2001 Oct;18(10):803-10. doi: 10.1046/j.1464-5491.2001.00577.x.
• Background Dwyer DS, Liu Y, Bradley RJ. Dopamine receptor antagonists modulate glucose uptake in rat pheochromocytoma (PC12) cells. Neurosci Lett. 1999 Oct 29;274(3):151-4. doi: 10.1016/s0304-3940(99)00712-0.
• Background Dwyer DS, Pinkofsky HB, Liu Y, Bradley RJ. Antipsychotic drugs affect glucose uptake and the expression of glucose transporters in PC12 cells. Prog Neuropsychopharmacol Biol Psychiatry. 1999 Jan;23(1):69-80. doi: 10.1016/s0278-5846(98)00092-x.
• Background Goldstein LE, Sporn J, Brown S, Kim H, Finkelstein J, Gaffey GK, Sachs G, Stern TA. New-onset diabetes mellitus and diabetic ketoacidosis associated with olanzapine treatment. Psychosomatics. 1999 Sep-Oct;40(5):438-43. doi: 10.1016/S0033-3182(99)71210-7. No abstract available.
• Background Hagg S, Joelsson L, Mjorndal T, Spigset O, Oja G, Dahlqvist R. Prevalence of diabetes and impaired glucose tolerance in patients treated with clozapine compared with patients treated with conventional depot neuroleptic medications. J Clin Psychiatry. 1998 Jun;59(6):294-9. doi: 10.4088/jcp.v59n0604.
• Background HAMILTON M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960 Feb;23(1):56-62. doi: 10.1136/jnnp.23.1.56. No abstract available.
• Background Henderson DC, Cagliero E, Gray C, Nasrallah RA, Hayden DL, Schoenfeld DA, Goff DC. Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: A five-year naturalistic study. Am J Psychiatry. 2000 Jun;157(6):975-81. doi: 10.1176/appi.ajp.157.6.975.
• Background Kay SR, Opler LA, Lindenmayer JP. Reliability and validity of the positive and negative syndrome scale for schizophrenics. Psychiatry Res. 1988 Jan;23(1):99-110. doi: 10.1016/0165-1781(88)90038-8.
• Background Khandoudi N, Delerive P, Berrebi-Bertrand I, Buckingham RE, Staels B, Bril A. Rosiglitazone, a peroxisome proliferator-activated receptor-gamma, inhibits the Jun NH(2)-terminal kinase/activating protein 1 pathway and protects the heart from ischemia/reperfusion injury. Diabetes. 2002 May;51(5):1507-14. doi: 10.2337/diabetes.51.5.1507.
• Background Lamberti JS, Bellnier T, Schwarzkopf SB. Weight gain among schizophrenic patients treated with clozapine. Am J Psychiatry. 1992 May;149(5):689-90. doi: 10.1176/ajp.149.5.689.
• Background Nuechterlein KH, Dawson ME, Gitlin M, Ventura J, Goldstein MJ, Snyder KS, Yee CM, Mintz J. Developmental Processes in Schizophrenic Disorders: longitudinal studies of vulnerability and stress. Schizophr Bull. 1992;18(3):387-425. doi: 10.1093/schbul/18.3.387.
• Background Newcomer JW, Haupt DW, Fucetola R, Melson AK, Schweiger JA, Cooper BP, Selke G. Abnormalities in glucose regulation during antipsychotic treatment of schizophrenia. Arch Gen Psychiatry. 2002 Apr;59(4):337-45. doi: 10.1001/archpsyc.59.4.337.
• Background Saltiel AR, Olefsky JM. Thiazolidinediones in the treatment of insulin resistance and type II diabetes. Diabetes. 1996 Dec;45(12):1661-9. doi: 10.2337/diab.45.12.1661.
• Background Segal DL, Hersen M, Van Hasselt VB. Reliability of the Structured Clinical Interview for DSM-III-R: an evaluative review. Compr Psychiatry. 1994 Jul-Aug;35(4):316-27. doi: 10.1016/0010-440x(94)90025-6.
• Background Skre I, Onstad S, Torgersen S, Kringlen E. High interrater reliability for the Structured Clinical Interview for DSM-III-R Axis I (SCID-I). Acta Psychiatr Scand. 1991 Aug;84(2):167-73. doi: 10.1111/j.1600-0447.1991.tb03123.x.
• Background Strachan MW, Deary IJ, Ewing FM, Frier BM. Is type II diabetes associated with an increased risk of cognitive dysfunction? A critical review of published studies. Diabetes Care. 1997 Mar;20(3):438-45. doi: 10.2337/diacare.20.3.438.
• Background Valdes CT, Elkind-Hirsch KE. Intravenous glucose tolerance test-derived insulin sensitivity changes during the menstrual cycle. J Clin Endocrinol Metab. 1991 Mar;72(3):642-6. doi: 10.1210/jcem-72-3-642.
• Background Ventura J, Liberman RP, Green MF, Shaner A, Mintz J. Training and quality assurance with the Structured Clinical Interview for DSM-IV (SCID-I/P). Psychiatry Res. 1998 Jun 15;79(2):163-73. doi: 10.1016/s0165-1781(98)00038-9.
• Background Wahlin A, Nilsson E, Fastbom J. Cognitive performance in very old diabetic persons: the impact of semantic structure, preclinical dementia, and impending death. Neuropsychology. 2002 Apr;16(2):208-16.
• Background Ware J Jr, Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care. 1996 Mar;34(3):220-33. doi: 10.1097/00005650-199603000-00003.
• Background Wirshing DA, Spellberg BJ, Erhart SM, Marder SR, Wirshing WC. Novel antipsychotics and new onset diabetes. Biol Psychiatry. 1998 Oct 15;44(8):778-83. doi: 10.1016/s0006-3223(98)00100-0.

Drugs

Indications