Lurasidone Effects on Tissue Glutamate in Schizophrenia

Study ID
STU 032012-053

Cancer Related
No

Healthy Volunteers
No

Study Sites

  • UT Southwestern-Other
  • UT Southwestern-Clinical Translational Research Center (CTRC)
  • Dallas Veteran's Affairs Medical Center
  • UT Southwestern Ambulatory Services
  • UT Southwestern University Hospital– Zale Lipshy

Contact
Debra Bushong
214-648-4653
debra.bushong@utsouthwestern.edu

Principal Investigator
Carol Tamminga

Summary

24 individuals with schizophrenia or schizoaffective disorders, who are currently considered stable, will be recruited, screened for entry criteria into a blinded study with a 2:1:1 randomization (lurasidone/haloperidol/perphenazine) to examine glutamate-related outcomes with lurasidone as compared to haloperidol and perphenazine. other medications can include SSRis, but not mood stabilizers. Zolpidem for sleep (prn) will be allowed but no other centrally active medications. Patients will be psychiatrically stable with no major change in symptoms within the past 8 weeks or PanSS fluctuation of [Greater Than]10% within the preliminary assessments. They will have had no hospitalization or suicidality thoughts in the past eight weeks. Patient volunteers will be medically healthy, diagnosed using the SCiD, and rated with standardized symptom scales (PanSS, CGi, BaS, and SaS). a brief assessment of medication adherence (BaRS) will be administered at baseline and Week 4. Clinical chemistry tests will be performed during screening to verify medical stability. each volunteer will be assessed with a standard cognition battery, the Brief assessment of Cognition in Schizophrenia (BaCS) and a web-based neurocognitive battery. each participant will undergo the specified glutamate outcome measures (below) at baseline and at the end of 4 weeks of treatment with study medication.
at study start all volunteers will be discontinued from their current antipsychotic medication (aPD) and switched to haloperidol 4mg for 5 days. at the end of this discontinuation period, all baseline symptom ratings and cognition testing will be done, as well as the baseline imaging procedures. at the end of the baseline procedures, volunteers will be blindly randomized, either to lurasidone at 40mg (n[?]12), or to haloperidol at 4mg/d or perphenazine at 16mg/d (n[?]12). Dose will increase to 80mg lurasidone, 8 mg/d haloperidol, or 32 mg/d of perphenazine at the beginning of week two. Dose should be stable for the last 3 weeks of treatment unless side effects are prominent, then the dose can be decreased to 40 lurasidone/4 haloperidol/16 perphenazine mg/d for optimal clinical management. The randomization strategy will be designed and implemented by the research pharmacist in four blocks of six volunteers; drug will be dispensed by the research pharmacy according to the randomization schedule. The randomization will be followed by a four week treatment period at optimal dose levels. on the last two days of the 4 week stable dosing period, the specified glutamate outcome measures will be completed (neuroimaging and cognitive testing) along with all the symptom outcome measures, testing for drug plasma levels, and usual blood safety measures. Patients will be seen weekly for clinical evaluation; suicidality will be monitored weekly. all medications other than study drugs will be discontinued, as much as possible, for the 24-48 hr assessment period. after the evaluation phase, patients will be cross-titrated back to their original treatment medication and dosing.
This design will generate outcomes from 12 patients on lurasidone vs. 12 patients on haloperidol/ perphenazine.

Participant Eligibility


* Subject greater than or equal to 18 years of age on the day informed consent is signed.

* Subject meets DSM-IV criteria for a primary diagnosis of schizophrenia or schizoaffective disorder as established by structured interview using the SCID-CT. The duration of the subject[Single Quote]s illness must be at least one year.

* Subject provides written informed consent and is willing and able to comply with the protocol in the opinion of the investigator.

* Subject must be judged by the investigator to be an appropriate candidate for switching current antipsychotic medication due to insufficient efficacy and/or safety or tolerability concerns.

* Outpatients, or subjects who are clinically stable (but symptomatic and/or intolerant of current antipsychotic treatment), are eligible for enrollment.

* Subject is judged by the investigator to have been
* clinically stable
* (non-acute phase of illness) for at least 8 weeks prior to baseline. All subjects must meet the following criteria:
o CGI-S less than or equal to 4 (at both screening and baseline)
o Dose of the pre-switch antipsychotic(s) has been stable ((+ or -) 50 %) for at least 28 days prior to screening (up to protocol specified maximum dose)
o No exacerbation of schizophrenia or schizoaffective disorder has occurred for at least 8 weeks prior to screening

* Subjects taking two antipsychotic medications (but not more) at screening are eligible for study inclusion. However, the antipsychotic medication determined to be
* secondary
* , based on investigator judgment, must be discontinued prior to randomization. All subjects must be on a single antipsychotic medication at randomization.

* Subject is not pregnant (must have a negative urine pregnancy test at screening) and is not planning pregnancy within the projected duration of the study.

* Female subject who is of reproductive potential agrees to remain abstinent or use adequate and reliable contraception throughout the study and for at least 30 days after the last dose of lurasidone has been taken. In the investigator[Single Quote]s judgment, the subject will adhere to this requirement.

Adequate contraception is defined as continuous use of either two barrier methods (e.g., condom and spermicide or diaphragm with spermicide) or a hormonal contraceptive.
Acceptable hormonal contraceptives include the following: a) contraceptive implant (such as Norplant(RegisteredTM)) implanted at least 90 days prior to baseline; b) injectable contraception (such as medroxyprogesterone acetate injection) given at least 14 days prior to baseline; or c) oral contraception taken as directed for at least 30 days prior to baseline.

Subject who is of non-reproductive potential, i.e., subject who is surgically sterile, has undergone tubal ligation, or is postmenopausal (defined as at least 12 months of spontaneous amenorrhea or between 6 and 12 months of spontaneous amenorrhea with follicle stimulating hormone concentrations within postmenopausal range as determined by laboratory analysis) are not required to remain abstinent or use adequate contraception.

* Subject is in good physical health on the basis of medical history, physical examination, and laboratory screening.

* Subject who requires concomitant medication treatment with the following agents may be included if the subject has been on stable doses for the specified times: 1) oral hypoglycemic: must be at a stable dose for at least 6 weeks prior to screening; 2) thyroid hormone replacement: must be at a stable dose for at least 90 days prior to randomization; 3) antihypertensive agents: must be at a stable dose for at least 30 days prior to screening.

* Eyesight corrected to 20-40 or better

* Able to read, speak, and understand English*