One-Year Trial of Oral Ziprasidone in Bipolar Patients With Metabolic Syndrome
- Registration Number
- NCT01113541
- Lead Sponsor
- Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
- Brief Summary
The purpose of this study is to explore the impact of Ziprasidone HCl on the distribution of metabolic syndrome (MS) risk factors in a population of Bipolar patients presenting with glucose intolerance, dyslipidemia and/or elevated waist circumference associated with their current antipsychotic medication.
- Detailed Description
The trial was terminated prematurely on December 14, 2010, due to inability to recruit the planned number of subjects and shifting organizational priorities. The decision to terminate the trial was not based on any safety or efficacy concerns.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 13
- Subject must present at least 2 of the following risk factors of MS at screening: Elevated waist circumference: >102 cm in men and >88 cm in women; Elevated triglycerides (TGs): ≥1.7 mmol/L (≥150 mg/dL); Reduced HDL-Cholesterol: <1.03 mmol/L (<40 mg/dL) in men and <1.3 mmol/L (<50 mg/dL) in women; Elevated fasting glucose: ≥ 5.6 mmol/L.
- According to the clinical judgment of the investigator, the risk factors for MS have developed in close temporal relationship to starting an antipsychotic medication.
- Substitution to a less metabolically disruptive antipsychotic medication is considered
- Subjects with contraindication(s) to the use of Ziprasidone according to Canadian prescribing information.
- Subjects with a history of treatment resistance.
- Subjects with any medical condition (e.g. pre-existing diabetes, pre-existing dyslipidemia, thyroid pathology) or taking any concomitant medication (e.g. topiramate or other weight loss-promoting agents, hypoglycemic agents, hypolipemic agents), that may confound the evaluation of the study drug.
- Body mass index ≥ 40 at baseline.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Active treatment (switch to oral Ziprasidone) Ziprasidone HCL (oral) -
- Primary Outcome Measures
Name Time Method Percentage of Participants Who Achieved a Reduction From Baseline of at Least 1 Risk Factor for Metabolic Syndrome (MS) at Week 52 or Premature Discontinuation Week 52 or Early Termination MS risks factors: elevated (el) waist circumference: ≥102 centimeters (cm) in men and ≥88 cm in women (Asian origin: ≥90 cm \[men\] and ≥80 cm \[women\]); el triglycerides: ≥1.7 millimoles per liter (mmol/L) (1≥50 milligrams per deciliter \[mg/dL\]); reduced high-density lipoprotein cholesterol (HDL-C): \<1.03 mmol/L (\<40 mg/dL) in men and \<1.3 mmol/L (\<50 mg/dL) in women; el fasting glucose: ≥5.6 mmol/L (≥100 mg/dL); and el systolic/diastolic blood pressure: systolic ≥130 millimeters of mercury (mmHg) and/or diastolic ≥85 mmHg. Responder = at least 1 less risk factor at endpoint than baseline.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Individual Risk Factors of Metabolic Syndrome (MS): Elevated Triglycerides Baseline, Week 4, Week 12, Week 52 MS risk factor elevated triglycerides defined as ≥1.7 millimoles per liter (mmol/L) (1≥50 mg/dL).
Change From Baseline in Ten-year Coronary Heart Disease (CHD) Risk According to Framingham Scoring System Baseline, Week 4, Week 52 Framingham scoring system risk factors: age (risk points range: -9 to 16), cholesterol (risk points range: 0 to 13), HDL cholesterol (risk points range: -1 to 2), smoking (risk points range: 0 to 9), and systolic blood pressure (risk points range: 0 to 6); total risk points range \<0 to ≥25, higher score indicates higher 10 year risk (range \<1% to ≥30% 10 year risk).
Change From Baseline in Leptin Baseline, Week 52 or Early Termination Mean Change From Baseline in the Number of Risk Factors of Metabolic Syndrome (MS) Baseline, Week 52 MS risks factors: elevated waist circumference: ≥102 cm in men and ≥88 cm in women (Asian origin: ≥90 cm \[men\] and ≥80 cm \[women\]); elevated triglycerides: ≥1.7 mmol/L (1≥50 mg/dL); reduced HDL-C: \<1.03 mmol/L (\<40 mg/dL) in men and \<1.3 mmol/L (\<50 mg/dL) in women; elevated fasting glucose: ≥5.6 mmol/L (≥100 mg/dL); and elevated systolic/diastolic blood pressure: systolic blood pressure ≥130 mm Hg and/or diastolic blood pressure ≥85 mm Hg.
Metabolic Syndrome (MS) Prevalence Baseline through Week 52 Percentage of participants at each visit defined as having metabolic syndrome (MS) based on the National Cholesterol Education Program (NCEP) Adult Treatment Panel III. MS = 3 or more of 5 characteristics: abdominal obesity, hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol, high blood pressure, and high fasting glucose.
Percentage of Participants With Individual Metabolic Syndrome (MS) Risk Factors Baseline through Week 52 MS risks factors = elevated waist circumference: ≥102 cm in men and ≥88 cm in women (Asian origin: ≥90 cm \[men\] and ≥80 cm \[women\]); elevated triglycerides: ≥1.7 mmol/L (1≥50 mg/dL); reduced HDL-C: \<1.03 mmol/L (\<40 mg/dL) in men and \<1.3 mmol/L (\<50 mg/dL) in women; elevated fasting glucose: ≥5.6 mmol/L (≥100 mg/dL); and elevated systolic/diastolic blood pressure: systolic blood pressure ≥130 mm Hg and/or diastolic blood pressure ≥85 mm Hg.
Change From Baseline in Individual Risk Factors of Metabolic Syndrome (MS): Reduced High-density Lipoprotein Cholesterol (HDL-C) Baseline, Week 4, Week 12, Week 52 MS risk factor reduced HDL-C defined as \<1.03 millimoles per liter (mmol/L) (\<40 mg/dL) in men and \<1.3 mmol/L (\<50 mg/dL) in women.
Change From Baseline in Insulin Levels Baseline, Week 52 or Early Termination Change From Baseline in Individual Risk Factors of Metabolic Syndrome (MS): Elevated Fasting Glucose Baseline, Week 4, Week 12, Week 52 MS risk factor elevated fasting glucose defined as ≥5.6 millimoles per liter (mmol/L) (≥100 mg/dL).
Change From Baseline in Body Mass Index (BMI) Baseline, Week 4, Week 12, Week 52 or Early Termination Body mass index = weight in kilograms (kg) / height in meters (m)\^2 .
Change From Baseline in Apolipoprotein B (ApoB) Levels Baseline, Week 52 or Early Termination Clinical Global Impression - Improvement (CGI-I) Subscale Score Week 52 or Early Termination CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected.
Change From Baseline in Drug Attitude Inventory (DAI) Week 28, Week 52 or Early Termination DAI, a 10-item scale to assess how the attitude of schizophrenia participants toward their medications may affect compliance. Respondents indicate 'true' or 'false' for each item. An overall calculated score ranged from -10 to 10, where a positive score indicated a positive subjective response (compliant), a negative score indicated non-compliance. Change: score at observation minus score at baseline.
Change From Baseline in the Percentage of Participants With Each Individual Metabolic Syndrome (MS) Risk Factor Baseline through Week 52 MS risks factors: elevated waist circumference: ≥102 cm in men and ≥88 cm in women (Asian origin: ≥90 cm \[men\] and ≥80 cm \[women\]); elevated triglycerides: ≥1.7 mmol/L (1≥50 mg/dL); reduced HDL-C: \<1.03 mmol/L (\<40 mg/dL) in men and \<1.3 mmol/L (\<50 mg/dL) in women; elevated fasting glucose: ≥5.6 mmol/L (≥100 mg/dL); and elevated systolic/diastolic blood pressure: systolic blood pressure ≥130 mm Hg and/or diastolic blood pressure ≥85 mm Hg.
Change From Baseline in Individual Risk Factors of Metabolic Syndrome (MS): Elevated Waist Circumference Baseline, Week 4, Week 12, Week 52 MS risk factor elevated waist circumference defined as ≥102 centimeters (cm) in men and ≥88 cm in women (Asian origin: ≥90 cm \[men\] and ≥80 cm \[women\]).
Change From Baseline in Individual Risk Factors of Metabolic Syndrome (MS): Elevated Systolic/Diastolic Blood Pressure Baseline, Week 4, Week 12, Week 52 MS risk factor elevated systolic/diastolic blood pressure defined as systolic blood pressure ≥130 millimeters of mercury (mm Hg) and/or diastolic blood pressure ≥85 mm Hg.
Change From Baseline in Corrected QT Interval (QTc): Fridericia's Heart Rate Correction Formula (QTcF) Baseline, Week 4, Week 52 or Early Termination QT interval is the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. QTc is the QT interval corrected for heart rate. Corrected QT interval using Fridericia's heart rate correction formula: QTcF = QT/RR\^1/3, where RR=RR interval in seconds.
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score Baseline, Week 4, Week 12, Week 28, Week 52 or Early Termination Measures the overall severity of depressive symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
Change From Baseline in Young Mania Rating Scale (YMRS) Baseline, Week 4, Week 12, Week 28, Week 52 or Early Termination 11-item scale that measures the severity of manic episodes from subject reported symptoms over previous 48 hours and clinical observation during interview. Four items (irritability, speech, thought content, disruptive-aggressive behaviour) are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining 7 items (elevated mood, increased motor activity-energy, sexual interest, sleep, language-thought disorder, appearance, insight) are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). YMRS total score range = 0 to 60.
Change From Baseline in European Quality of Life (EuroQol) Visual Analogue Scale (EQ-5D VAS): Current Health State Score Baseline, Week 28, Week 52 or Early Termination EQ-5D: subject rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state.
Number of Participants With Suicidal Tendencies (Columbian-Suicide Severity Rating Scale, [C-SSRS], Mapped to C-CASA [Columbia Classification Algorithm For Suicide Assessment]) Baseline, Week 1 through Week 52 or Early Termination C-SSRS is a participant rated questionnaire to assess suicidal ideation, suicidal behavior, actual attempts (yes or no responses), and intensity of ideation (rated 1=low severity to 5=high severity). Yes/No responses are mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) categories: Completed suicide, suicide attempt, preparatory acts toward imminent suicidal behavior, suicidal ideation, and self-injurious behavior, or no suicidal intent. A participant could have a yes or no response in more than one category.
Change From Baseline in Total Cholesterol and Low-density Lipoprotein (LDL) Cholesterol Levels Baseline, Week 52 or Early Termination Change From Baseline in Weight Baseline, Week 4, Week 12, Week 52 or Early Termination Change From Baseline in Glycosylated Hemoglobin (HbA1c) Baseline, Week 52 or Early Termination Change From Baseline in Clinical Global Impression - Severity (CGI-S) Subscale Baseline, Week 4, Week 12, Week 28, Week 52 or Early Termination CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected.
Change From Baseline in Social and Occupational Functioning Assessment Scale (SOFAS) Baseline, Week 28, Week 52 or Early Termination 0-100 single score scale focusing exclusively on participant's level of social and occupational functioning; not directly influenced by overall severity of participant's psychological symptoms; higher score = higher level of functioning. 1 to 10 = persistent inability to maintain minimal personal hygiene; unable to function without harming self or others or without considerable external support; 91 to 100 = superior functioning in a wide range of activities.
Change From Baseline in EuroQoL Index (EQ-I) Baseline, Week 28, Week 52 or Early Termination EQ-5D: subject rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (confined to bed). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.
Change From Baseline in Impact of Weight on Quality of Life-Lite Version (IWQOL-Lite) Scale Baseline, Week 28, Week 52 or Early Termination 31-item self report inventory to assess impact of weight on quality of life. Five subscales: physical functioning, self-esteem, sexual life, public distress, and work, with categories in each subscale scored 1 (no trouble or difficulty) to 5 (persistent trouble or difficulty). The rescaled IWQoL-Lite score is determined by the sum of scores on all 31 items and rescaling this sum to a 1 to 100 scoring with 0=the poorest and 100=the best quality of life.
Change From Baseline in Physical Activity Index Baseline, Week 28, Week 52 or Early Termination Physical activity (exercise) score derived for each participant based on the frequency and intensity of physical activities: regular walking, recreational activity, cycling, and sporting activity. Six categories of total score: inactive (range: 0-2), occasional (range: 3-5), light (range: 6-8), moderate (range: 9-12), moderately vigorous (range: 13-20), and vigorous (≥21). Higher score = higher frequency and intensity of physical activity.
Trial Locations
- Locations (10)
Edgeland Medical, Dr. Alla Kirshner Medical Corporation
🇨🇦Winnipeg, Manitoba, Canada
Country Club Plaza
🇨🇦Winnipeg, Manitoba, Canada
Mental Health Centre for Research and Education
🇨🇦Calgary, Alberta, Canada
Office of Dr. A. K. Munshi
🇨🇦Sydney, Nova Scotia, Canada
Centre de recherche Fernand-Seguin de l'hopital Louis H. Lafontaine
🇨🇦Montreal, Quebec, Canada
Clinique St-Leonard
🇨🇦Montreal, Quebec, Canada
Capital, Health Authority, QE II Health Sciences Centre, Mood Disorder Clinic
🇨🇦Halifax, Nova Scotia, Canada
Diex Research Sherbrooke Inc.
🇨🇦Sherbrooke, Quebec, Canada
Foothills Medical Centre, Department of Psychiatry
🇨🇦Calgary, Alberta, Canada
Dr. Alexander McIntyre Inc.
🇨🇦Penticton, British Columbia, Canada