Schizoaffective Disorder, Schizophrenia, Schizophreniform Disorders
Conditions
Keywords
schizophrenia, metabolism, antipsychotics, diabetes, rozerem
Brief summary
This study involves people who have schizophrenia or schizoaffective disorder who are currently taking antipsychotic medications. Some antipsychotic medications may cause weight gain and may increase the risk of diabetes mellitus and heart disease.The purpose of this study is to find out what happens if another medication (ramelteon) is used along with your antipsychotic medication. We want to find out whether doing this will: * Change the way your body breaks down fat and sugar. * Affect your waist size, stomach fat and triglycerides (a type of fat in your blood). * Improve how your body responds to insulin. * Affect your quality of sleep. * Reduce movement disturbances Ramelteon is approved by the U.S. Food and Drug Administration (FDA) to treat people that have difficulty falling asleep. It is not approved for such things as affecting waist size or improving how the body breaks down fat and sugar. Its use in this study is investigational.
Detailed description
This is an 8-week randomized, double blind, placebo-controlled pilot study with 4- week follow up assessment, of ramelteon 8 mg/day, administered to subjects for 8 consecutive weeks as an adjunctive therapy in 40 non-diabetic schizophrenia subjects to examine ramelteon effects on body composition, glucose and lipid metabolism, sleep quality and symptoms of tardive dyskinesia using the Massachusetts General Hospital General Clinical Research Center. As far as we know, no previous study has been done to explore the potential role of ramelteon in improving metabolic, sleep, and movement disturbances in schizophrenia subjects. The novel approach of adjunctive ramelteon treatment in the schizophrenia population is promising.
Interventions
DRUGRamelteon
Two week supply of ramelteon 8mg/day first dispensed at baseline. New two week supply of study medication dispensed at each biweekly visit for 8 consecutive weeks.
DRUGPlacebo
Two week supply of placebo tablets first dispensed at baseline. New two week supply of placebo dispensed at each biweekly visit for 8 consecutive weeks.
Sponsors
Takeda
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* diagnosis of schizophrenia, schizoaffective disorder, any subtype or schizophreniform disorder * male or female, age 18-65 years * treatment with clozapine, olanzapine, quetiapine or risperidone * well established compliance with medications * Body Mass Index (BMI) of \> 27 Kg/m² with any component of metabolic syndrome or insulin resistance or a BMI of \> 30 Kg/m²:
Exclusion criteria
* inability to provide informed consent * substance and alcohol abuse * significant medical illness, including congestive heart failure, severe hepatic impairment, severe Chronic Obstructive Pulmonary Disease (COPD), severe sleep apnea, severe cardiovascular disease or renal disease * current history of diabetes mellitus or thyroid disease * women who are pregnant, breastfeeding, or who are unwilling or unable to use an effective form of birth control during the entire study * psychiatrically unstable, patients with major depression * patients treated with medications known to affect glucose tolerance such as birth control pills containing norgestrel, steroids, beta blockers, anti-inflammatory drugs (including daily aspirin and ibuprofen), thiazide diuretics; and agents that induce weight loss will be excluded from the study * treatment with fluvoxamine in the or ketoconazole past two weeks * treatment with fluconazole (a strong CYP2C9 inhibitor). * subjects treated with ziprasidone and aripiprazole conventional agents * treatment with sedative-hypnotics such as barbiturates, zolpidem, eszopiclone, zaleplon. The use of stable daily doses of benzodiazepines is allowed. * known hypersensitivity to ramelteon or any of its components
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Waist Circumference | Baseline and Week 8 | A comparison between the ramelteon group and the placebo group in change in waist circumference (measured in cm) measured at Baseline and Week 8. |
| Change in Insulin Resistance as Measured by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). | Baseline and Week 8 | A comparison between the ramelteon group and the placebo group of change in insulin resistance measured by the homeostatic model assessment of insulin resistance (HOMA-IR), assessed at Baseline and Week 8. |
| Change in Abdominal Fat (DEXA). | Baseline and Week 8 | A comparison between the ramelteon group and the placebo group of change in abdominal fat measured by a DEXA scan, assessed at Baseline and Week 8. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from the Freedom Trial Clinic at the Erich Lindemann Mental Health Center and were studied at the Mallinckrodt General Clinical Research Center (GCRC) at the Massachusetts General Hospital (MGH), Boston
Pre-assignment details
After providing written informed consent, subjects underwent a diagnostic evaluation by a research psychiatrist using the Structured Clinical Interview for DSM-IV (SCID). All subjects were screened and enrolled based on eligibility criteria. Baseline study assessments were completed prior to intervention.
Participants by arm
| Arm | Count |
|---|---|
| Ramelteon | 14 |
| Placebo sugar pill | 6 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | Ramelteon | Total | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 20 Participants | 6 Participants |
| Age Continuous | 49 years STANDARD_DEVIATION 7 | 53 years STANDARD_DEVIATION 8 | 56 years STANDARD_DEVIATION 9 |
| Region of Enrollment United States | 14 participants | 20 participants | 6 participants |
| Sex: Female, Male Female | 6 Participants | 7 Participants | 1 Participants |
| Sex: Female, Male Male | 8 Participants | 13 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 16 | 0 / 9 |
| serious Total, serious adverse events | 0 / 16 | 0 / 9 |
Outcome results
Primary
Change in Abdominal Fat (DEXA).
A comparison between the ramelteon group and the placebo group of change in abdominal fat measured by a DEXA scan, assessed at Baseline and Week 8.
Time frame: Baseline and Week 8
Population: The number of participants for analysis (intent to treat) were those that completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon | Change in Abdominal Fat (DEXA). | 3934.86 g | Standard Deviation 1151.97 |
| Placebo (Sugar Pill) | Change in Abdominal Fat (DEXA). | 5120.92 g | Standard Deviation 1770.58 |
Primary
Change in Insulin Resistance as Measured by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR).
A comparison between the ramelteon group and the placebo group of change in insulin resistance measured by the homeostatic model assessment of insulin resistance (HOMA-IR), assessed at Baseline and Week 8.
Time frame: Baseline and Week 8
Population: The number of participants for analysis (intent to treat) were those that completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon | Change in Insulin Resistance as Measured by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). | 2.4 HOMA score | Standard Deviation 1.51 |
| Placebo (Sugar Pill) | Change in Insulin Resistance as Measured by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). | 2.36 HOMA score | Standard Deviation 1.73 |
Primary
Change in Waist Circumference
A comparison between the ramelteon group and the placebo group in change in waist circumference (measured in cm) measured at Baseline and Week 8.
Time frame: Baseline and Week 8
Population: The number of participants for analysis (intent to treat) were those that completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon | Change in Waist Circumference | 106.09 cm | Standard Deviation 8.8 |
| Placebo (Sugar Pill) | Change in Waist Circumference | 108.37 cm | Standard Deviation 6.5 |