Double Blind Placebo Controlled Investigation of Amantadine for Retarding Weight Gain in First Episode Adlt Psychotic Subjects Beginning Therapy With Olanzapine.
Screening: Screening will include demographics, medical and psychiatric histories and a
clinical interview to determine psychiatric diagnosis. Screening will also include a
physical examination and laboratory assessments (CBC, electrolytes, kidney function, liver
function, TSH) to rule out concurrent medical illness that could be a contraindication to
amantadine treatment. Blood will also be drawn for fasting lipid profile, glucose, insulin,
C reactive protein, adiponectin, and leptin. Subjects will also have the option of allowing
us to draw 2 additional tubes for as yet to be determined studies, not to include HIV or
genetic testing. Subjects will also have the option of allowing us to draw 1 additional tube
for platelet-specific protein assay, termed SEPT5. The rationale for measuring SEPT5 levels
is to test a hypothesis that individuals with clinically-defined mental disorders have
altered levels of this protein in their circulating blood platelets. A urine drug screen
will be performed.
Phase 1: Subjects may enter Phase 1 within the first 12 weeks of treatment with olanzapine.
At entry into Phase 1, anthropometric measurements will be taken (height, weight, waist and
hip circumference) and BMI calculated. Baseline assessments will include questionnaires
about hunger (to be done in the fasting state) (Subjective Satiety Scale), and activity
(Baeckea Activity Questionnaire), respiratory quotient (RQ) and resting energy expenditure
(REE) assessed using the Medgraphics metabolic cart, and body composition determined by dual
x-ray absorptiometry (DXA, Hologic Delphia). Prior to every DXA scan Body Composition Lab
personnel will administer a safety questionnaire and women of reproductive age will have a
blood pregnancy test. Visits will be scheduled weekly to monitor weight and to provide
healthy lifestyle counseling based on the Solutions for Wellness program developed by Lilly.
During the first 3 weeks, subjects will be called by research personnel once per week to
complete a 24 hour diet recall by phone. During the first 4 weeks of the study, RQ and
capillary glucose will be repeated weekly since it is anticipated that changes to these
parameters may occur early on. At monthly intervals clinical interviews will monitor for
changes in psychosis and blood pressure will be assessed. When subjects gain 1 BMI unit,
fasting bloodwork and baseline assessments are repeated and they are enrolled in Phase 2.
Subjects who do not gain 1 BMI unit within 12 weeks of olanzapine treatment will end study
participation at the end of Phase 1.
Phase 2: Subjects may enter Phase 2 following Phase 1 or enter directly if there is
documentation of more than 1 but less than 3 BMI units of weight gain and they have started
olanzapine within the previous 12 weeks. Phase 2 is a double blind placebo controlled
addition of amantadine to ongoing olanzapine therapy. All subjects entering Phase 2 will
have anthropometric measurements, and BMI will be calculated. Fasting lipid profile,
glucose, insulin, C reactive protein, adiponectin, and leptin will be obtained, as will
liver function tests and a urine drug screen. Body composition by DXA as well as RQ and REE
will be determined. Prior to every DXA scan the Body Composition Lab will administer a
safety questionnaire and women of reproductive age will have a pregnancy test. A Food
Propensity questionnaire will be administered to document recent trends in food choices, and
the exercise and hunger questionnaires will also been done. Following completion of baseline
assessments, randomization to amantadine or placebo will occur. Subjects will begin taking 1
capsule daily for 2 days, 2 capsules daily for 5 days, and then 3 capsules daily. Amantadine
capsules will each contain 100 mg of amantadine. Clinical state and emergence of side
effects, including orthostatic hypotension, will be monitored at all visits by research
clinicians. If subjects experience mild side effects with increase in number of capsules,
the titration will be slowed. During Phase 2, subjects will be called by research personnel
on 3 nonconsecutive days to complete a 24 hour diet recall by phone. Biweekly, all subjects
will meet with a study physician or nurse for standardized healthy lifestyle counseling
based on the Solutions for Wellness program available from Lilly. BMI will be calculated
biweekly and baseline measures will be repeated at the final study visit. Urine pregnancy
test will be performed monthly on all women. When subjects gain an additional 3 BMI units
(approximately 15 lbs), or when they complete 16 weeks of double blind medication they will
repeat all Visit 13 measures and end study participation.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
To compare time to clinical significant weight gain in the amantadine + olanzapine group with the placebo + olanzapine group.
Karen A Graham, MSc MD
University of North Carolina, Chapel Hill
United States: Institutional Review Board
|University of North Carolina at Chapel Hill||Chapel Hill, North Carolina 27599|