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

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 4


Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

Genetics Home Reference related topics: schizophrenia

MedlinePlus related topics: Schizophrenia

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

U.S. FDA Resources

Further study details as provided by David C. Henderson, MD, Harvard Medical School:

Primary Outcome Measures:

Change From Baseline in Fasting Glucose [ Time Frame: baseline, week 6 ]
Subjects on clozapine with adjunctive ziprasidone were compared to subjects on olanzapine with adjunctive ziprasidone on change in fasting glucose levels from baseline to study endpoint (week 6 - baseline)
Change From Baseline on Fasting Insulin [ Time Frame: baseline, week 6 ]
Subjects on clozapine with adjunctive ziprasidone were compared to subjects on olanzapine with adjunctive ziprasidone on change in fasting insulin levels from baseline to study endpoint (week 6 - baseline)


Enrollment:	24
Study Start Date:	January 2005
Study Completion Date:	March 2007

Show Detailed Description

Eligibility


Ages Eligible for Study:	18 Years to 65 Years (Adult)
Sexes Eligible for Study:	All
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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.

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.

Hägg S, Joelsson L, Mjörndal 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.

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.

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.

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.

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.


Responsible Party:	David C. Henderson, MD, Associate Professor of Psychiatry, Harvard Medical School
ClinicalTrials.gov Identifier:	NCT00351000 History of Changes
Other Study ID Numbers:	1-2005
Study First Received:	July 11, 2006
Results First Received:	December 20, 2012
Last Updated:	November 16, 2016

Keywords provided by David C. Henderson, MD, Harvard Medical School:


Schizophrenia Ziprasidone Diabetes Insulin Resistance

Additional relevant MeSH terms:


Diabetes Mellitus Schizophrenia Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Schizophrenia Spectrum and Other Psychotic Disorders Mental Disorders Ziprasidone Clozapine Olanzapine Serotonin Antagonists Serotonin Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs	Antipsychotic Agents Tranquilizing Agents Central Nervous System Depressants Psychotropic Drugs Dopamine Antagonists Dopamine Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Gastrointestinal Agents Serotonin Uptake Inhibitors Neurotransmitter Uptake Inhibitors Membrane Transport Modulators GABA Antagonists GABA Agents

ClinicalTrials.gov processed this record on June 22, 2017