Clinical trial NCT00903916: Effect of Antipsychotics on Appetite Regulation
Official title: Effect of Weight-increasing Psychotropic Medications on Appetite Regulation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Psychotic Disorders
Keywords: antipsychotic
ghrelin
PYY
appetite
weight gain
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2009-05-19
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: patients ages 18 to 40 years of age who are early in treatment (i.e., started treatment in the past month) with 1 of 4 antipsychotic medications (olanzapine, risperidone, ziprasidone, aripiprazole)

Brief summary: The purpose of this study is to evaluate changes in appetite-regulating hormones, body composition (weight, body fat%), and hunger ratings in persons early in treatment with one of four atypical antipsychotic medications (olanzapine, risperidone, ziprasidone, aripiprazole).

Detailed description: Severe weight gain and glucose dysregulation are serious problems in patients treated with second-generation ('atypical') antipsychotics (SGA). These side effects frequently interfere with medication compliance and necessitate discontinuation of treatment. Although the causal mechanisms for weight and glucose dysregulation are not well understood, one promising area of investigation targets SGA-induced disturbances in appetite and in appetite-regulating hormones. Findings from our group (and others) demonstrate SGA treatment-related increases in fasting levels of the appetite-stimulating hormone, ghrelin, as well as increases in self-report hunger. This novel study will examine prospective changes in ghrelin and in the 'satiety-signaling' peptide YY (PYY) as measured before and after participants consume a standard mixed-macronutrient meal. Data are obtained at baseline (within 4 weeks of beginning medication), and again 2 months and 4 months later.

Eligibility criteria: Inclusion Criteria:

1. Meets DSM IV criteria for a psychotic disorder (schizophrenia, schizophreniform, brief psychotic disorder, schizoaffective disorder), bipolar disorder, or major depression with psychotic features;
2. "Drug naïve" prior to most recent psychiatric diagnosis;
3. Currently prescribed one of four atypical antipsychotic medications: olanzapine, risperidone, ziprasidone, or aripiprazole;
4. Between the ages of 18 and 40, any race and either gender;
5. Not obese (BMI \< 30 kg/m2) (fasting and postprandial ghrelin levels are altered in obesity);
6. Has negative histories for cardiovascular, metabolic, and endocrine disorders at screening;
7. Is willing and able to eat animal-derived foods; and
8. Is not exercising 3 or more times per week.

Exclusion Criteria:

1. Use of medications to treat metabolic and endocrine abnormalities, corticosteroids, over-the-counter appetite suppressants that contain phentermine or Sibutramine;
2. Active involvement with a weight loss program (i.e., Weight Watchers);
3. Serious or unstable medical illness which requires ongoing treatment with medication (this does not include hypertension);
4. Anemia;
5. At serious suicidal risk;
6. Current substance abuse or dependence;
7. For female subjects, pregnancy or nursing (because pregnancy may influence appetite and because the body composition procedure involves low level X-ray exposure).
8. Known history of mental retardation or dementia.
9. Children and adolescents under age 18 will be excluded owing to the inherent confounding effects of normal growth on body weight and appetite.

Primary outcomes:
measure: ghrelin area under the curve
timeFrame: baseline, 2 and 4 months
measure: PYY area under the curve
timeFrame: baseline, 2 and 4 months
Secondary outcomes:
measure: glucose area under the curve
timeFrame: baseline, 2 and 4 months
measure: insulin area under the curve
timeFrame: baseline, 2 and 4 months
measure: body composition
timeFrame: baseline, 2 and 4 months
measure: subjective appetite ratings
timeFrame: baseline, 2 and 4 months
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Kimberly A Brownley, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Graham KA, Cho H, Brownley KA, Harp JB. Early treatment-related changes in diabetes and cardiovascular disease risk markers in first episode psychosis subjects. Schizophr Res. 2008 Apr;101(1-3):287-94. doi: 10.1016/j.schres.2007.12.476. Epub 2008 Feb 5.
citation: Graham KA, Perkins DO, Edwards LJ, Barrier RC Jr, Lieberman JA, Harp JB. Effect of olanzapine on body composition and energy expenditure in adults with first-episode psychosis. Am J Psychiatry. 2005 Jan;162(1):118-23. doi: 10.1176/appi.ajp.162.1.118.