Ziprasidone for Clozapine- or Olanzapine-Associated Diabetes Mellitus - Full Text View

Sponsors and Collaborators:	North Suffolk Mental Health Association Pfizer
Information provided by:	North Suffolk Mental Health Association
ClinicalTrials.gov Identifier:	NCT00351000

Purpose

This study is a six-week, open label trial of the novel antipsychotic agent, ziprasidone, added to a stable dose of clozapine or olanzapine in 40 diabetes mellitus patients, patients with an impaired fasting glucose or insulin resistance with schizophrenia or schizoaffective disorder. The first two weeks will be a fixed-dose of ziprasidone 40 mg twice a day. During weeks 2-6, the ziprasidone dose may be increased up to 80 mg twice a day.

Condition	Intervention	Phase
Schizophrenia	Drug: Ziprasidone	Phase IV

MedlinePlus related topics: Diabetes Schizophrenia

Drug Information available for: Insulin Olanzapine Ziprasidone Ziprasidone hydrochloride Ziprasidone mesylate Dextrose Clozapine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study
Official Title:	An Open Label Trial of Ziprasidone as an Adjuvant for Clozapine- or Olanzapine-Associated Diabetes Mellitus or Impaired Fasting Glucose in Chronic Schizophrenia

Further study details as provided by North Suffolk Mental Health Association:

Primary Outcome Measures:

Evaluate the effects of ziprasidone on weight, BMI, waist/hip circumference, fasting glucose, fasting insulin, lipids, dietary and activity level.
Evaluate whether ziprasidone improves glucose and lipid metabolism in diabetic or impaired fasting glucose clozapine- or olanzapine-treated subjects.
Evaluate tolerability and safety of ziprasidone added to clozapine or olanzapine using the SAFTEE, vital signs, and EKG.
Evaluate the effects of ziprasidone upon negative symptoms using the SANS total score.
Evaluate the effects of ziprasidone upon positive symptoms and depressive symptoms using the PANSS total score, positive symptom subscale and Hamilton Depression Rating Scale.

Estimated Enrollment:	40
Study Start Date:	January 2005
Study Completion Date:	March 2007

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Diagnosis of Schizophrenia, any subtype or schizoaffective disorder
Ages 18-65 years
Capable of providing informed consent
Antipsychotic Agents –associated diabetes mellitus, impaired fasting glucose or insulin resistance
Stable dose of clozapine or olanzapine for at least 1 month
Optimal dose of clozapine or olanzapine, or a maximal dose if limited by significant side effects

Exclusion Criteria:

Serious medical or neurological illness (unstable cardiac disease including recent myocardial infarction or heart failure, seizure disorder, malignancy, liver or renal impairment, etc.)
Current substance abuse
Pregnancy, nursing, or unwilling to use appropriate birth control measures during participation if female and fertile
History of serious blood dyscrasia requiring discontinuation of clozapine
Serious suicidal or homicidal risk within the past six months
History of diabetes mellitus prior to treatment with clozapine or olanzapine
H/o prolongation of QTc interval (>450) on EKG or clinically significant EKG abnormalities.
Treatment with medications that significantly prolong QTc interval such as dofetilde, sotalol, quinidine, class Ia and III antiarrhythmics, mesoridazine, thioridazine, chlorpromazine, droperidol, pimozide, sparfloxacin, gatifloxacin, moxifloxacine, halofantrine, mefloquine, pentamidine, arsenic trioxide, levomethadyul acetate, dolasetron myselate, probucol, or tacrolimus.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00351000

Locations

United States, Massachusetts
Freedom Trail Clinic
Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

North Suffolk Mental Health Association

Pfizer

Investigators

Principal Investigator:

David C Henderson, MD

North Suffolk Mental Health Association

More Information

Publications:

Alao AO, Malhotra K, Dewan MJ. Comparing the side effect profile of the atypical antipsychotics. West Afr J Med. 2002 Oct-Dec;21(4):313-5. Review.

Allison DB, Mentore JL, Heo M, Chandler LP, Cappelleri JC, Infante MC, Weiden PJ. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry. 1999 Nov;156(11):1686-96. Review.

Ananth J, Venkatesh R, Burgoyne K, Gunatilake S. Atypical antipsychotic drug use and diabetes. Psychother Psychosom. 2002 Sep-Oct;71(5):244-54.

Baptista T, Kin NM, Beaulieu S, de Baptista EA. Obesity and related metabolic abnormalities during antipsychotic drug administration: mechanisms, management and research perspectives. Pharmacopsychiatry. 2002 Nov;35(6):205-19. Review.

Caro JJ, Ward A, Levinton C, Robinson K. The risk of diabetes during olanzapine use compared with risperidone use: a retrospective database analysis. J Clin Psychiatry. 2002 Dec;63(12):1135-9.

Cohen S, Fitzgerald B, Okos A, Khan S, Khan A. Weight, lipids, glucose, and behavioral measures with ziprasidone treatment in a population with mental retardation. J Clin Psychiatry. 2003 Jan;64(1):60-2.

Colli A, Cocciolo M, Francobandiera F, Rogantin F, Cattalini N. Diabetic ketoacidosis associated with clozapine treatment. Diabetes Care. 1999 Jan;22(1):176-7. No abstract available.

Daniel DG, Copeland LF. Ziprasidone: comprehensive overview and clinical use of a novel antipsychotic. Expert Opin Investig Drugs. 2000 Apr;9(4):819-28. Review.

Gianfrancesco FD, Grogg AL, Mahmoud RA, Wang RH, Nasrallah HA. Differential effects of risperidone, olanzapine, clozapine, and conventional antipsychotics on type 2 diabetes: findings from a large health plan database. J Clin Psychiatry. 2002 Oct;63(10):920-30.

Goodnick PJ. Ziprasidone: profile on safety. Expert Opin Pharmacother. 2001 Oct;2(10):1655-62. Review.

Green MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry. 1996 Mar;153(3):321-30. Review.

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.

HAMILTON M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960 Feb;23:56-62. No abstract available.

Henderson DC, Goff DC. Risperidone as an adjunct to clozapine therapy in chronic schizophrenics. J Clin Psychiatry. 1996 Sep;57(9):395-7.

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.

Kato MM, Goodnick PJ. Antipsychotic medication: effects on regulation of glucose and lipids. Expert Opin Pharmacother. 2001 Oct;2(10):1571-82. Review.

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.

Koller E, Schneider B, Bennett K, Dubitsky G. Clozapine-associated diabetes. Am J Med. 2001 Dec 15;111(9):716-23.

Koller EA, Doraiswamy PM. Olanzapine-associated diabetes mellitus. Pharmacotherapy. 2002 Jul;22(7):841-52. Review.

Levine J, Schooler NR. SAFTEE: a technique for the systematic assessment of side effects in clinical trials. Psychopharmacol Bull. 1986;22(2):343-81. No abstract available.

Melkersson KI, Hulting AL, Brismar KE. Elevated levels of insulin, leptin, and blood lipids in olanzapine-treated patients with schizophrenia or related psychoses. J Clin Psychiatry. 2000 Oct;61(10):742-9.

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. Review.

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.

Opp D, Hildebrandt C. Olanzapine-associated type 2 diabetes mellitus. Schizophr Res. 2002 Jul 1;56(1-2):195-6. No abstract available.

Pi-Sunyer FX. Medical hazards of obesity. Ann Intern Med. 1993 Oct 1;119(7 Pt 2):655-60. Review.

Seaburg HL, McLendon BM, Doraiswamy PM. Olanzapine-associated severe hyperglycemia, ketonuria, and acidosis: case report and review of literature. Pharmacotherapy. 2001 Nov;21(11):1448-54. Review.

Spivak B, Alamy SS, Jarskog LF, Sheitman BB, Lieberman JA. Ziprasidone alternative for olanzapine-induced hyperglycemia. Am J Psychiatry. 2002 Sep;159(9):1606. No abstract available.

Taylor D. Ziprasidone in the management of schizophrenia : the QT interval issue in context. CNS Drugs. 2003;17(6):423-30. Review.

Wetterling T. Bodyweight gain with atypical antipsychotics. A comparative review. Drug Saf. 2001 Jan;24(1):59-73. Review.

Wilson DR, D'Souza L, Sarkar N, Newton M, Hammond C. New-onset diabetes and ketoacidosis with atypical antipsychotics. Schizophr Res. 2003 Jan 1;59(1):1-6.

Study ID Numbers:	1-2005
Study First Received:	July 11, 2006
Last Updated:	April 19, 2007
ClinicalTrials.gov Identifier:	NCT00351000
Health Authority:	United States: Institutional Review Board

Keywords provided by North Suffolk Mental Health Association:

Schizophrenia
Ziprasidone
Diabetes
Insulin Resistance

Study placed in the following topic categories:

Metabolic Diseases
Diabetes Mellitus
Olanzapine
Endocrine System Diseases
Serotonin
Insulin
Schizophrenia
Dopamine
Mental Disorders

Clozapine
Psychotic Disorders
Insulin Resistance
Endocrinopathy
Glucose Metabolism Disorders
Metabolic disorder
Ziprasidone
Schizophrenia and Disorders with Psychotic Features

Additional relevant MeSH terms:

Neurotransmitter Agents
Tranquilizing Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Psychotropic Drugs
Central Nervous System Depressants
Dopamine Antagonists

Antipsychotic Agents
Pharmacologic Actions
Serotonin Antagonists
Serotonin Agents
Therapeutic Uses
Dopamine Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 14, 2009