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A Double-blind, Placebo Controlled Trial of Risperidone for the Treatment of Anorexia Nervosa

This study has been completed.
Sponsor:
Collaborators:
Janssen Pharmaceuticals
National Center for Research Resources (NCRR)
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT00140426
First received: August 31, 2005
Last updated: December 29, 2015
Last verified: December 2015
  Purpose

The aim of this pilot study is to determine the safety and efficacy of risperidone for the treatment of anorexia nervosa.

Hypothesis 1: Subjects on risperidone will show a more significant decrease in body image distortion and Eating Disorder Inventory -2 scores than subjects on placebo.

Hypothesis 2: Subjects on risperidone will reach and maintain at or above 90% Ideal body weight sooner than controls.


Condition Intervention Phase
Anorexia Nervosa
Drug: Risperidone
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-blind, Placebo Controlled Trial of Risperidone for the Treatment of Anorexia Nervosa

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Change in Eating Disorder Inventory-2 Drive for Thinness Subscale (DT) [ Time Frame: month ] [ Designated as safety issue: No ]

    Eating Disorder Inventory -2 - Subscale : Drive for Thinness Subscale (DT). Lower scores are better on this scale and indicate less cognitive focus on drive for thinness.

    The EDI 2 is a 91 item scale with 8 subscales - (Drive for thinness, Bulimia, body dissatisfaction, ineffectiveness, perfection, interpersonal distrust, interoceptive awareness and maturity fears.). The DT subscale was used for this outcome. Respondents rate each item as "usually , often, sometimes, rarely or never". Subscale scores are computed by summing all item scores for each subscale. There are 7 items in the DT subscale (questions 1,7,11,16,25,32 and 49). the subscale score range is 0-21. The EDI-2 was completed by subjects at baseline and then monthly during study participation (range 0 -18 weeks). Change in the DT subscale score was calculated using an estimate of change in score between week 0 and week 7 derived from the mixed effect model across all time points.


  • Change in Eating Disorder Inventory (EDI)-2 Score for Body Dissatisfaction (BD) [ Time Frame: monthly ] [ Designated as safety issue: No ]

    change in Eating Disorder Inventory (EDI) 2-score for Body Dissatisfaction (BD).

    Lower scores are better on this scale. Higher scores indicate the subject has greater body dissatisfaction. BD is one of the 8 subscales of the EDI-2. 9 of the 91 questions in the EDI-2 scale constitute this subscale. The score range is 0-27. Subjects completed the EDI-2 at baseline and monthly during study participation (range 0 to 18 weeks). Change in the BD subscale score during the study was calculated using an estimate of change in score between week 0 and week 7 derived from the mixed effect model across all time points.


  • Hazard Ratio for Time to Reaching Ease Of Eating Level 3 From Start of Study (Normal Eating Behavior) [ Time Frame: weekly up to study endpoint: reaching target weight and maintaining for 1 month ] [ Designated as safety issue: No ]

    The Ease of Eating Scale (EOES) is a 14 item scale which measures Food avoidance behaviors (FABs). The scale is rated by staff observing a subject eating a meal or snack. 0 = normal eating behavior, maximum score 28.

    Higher scores indicate more food avoidance behaviors, such as taking small bites, taking > 30 seconds between bites (slow eating), etc.

    EOE was completed for each meal a subject ate in the program and scores were averaged for each week in the study and entered in the data base.

    Change in EOES score was calculated by evaluating change over time. This measure was only used in Phase 1 of the study, for days the subjects were in the treatment program.


  • Color A Person Test (CAPT) [ Time Frame: monthly ] [ Designated as safety issue: No ]

    Color A Person Test (CAPT) - Subjects color an outlined image of a body to indicate body dissatisfaction (red (5)= very dissatisfied, Yellow, dissatisfied, black, neutral, green satisfied, blue very satisfied (1). The outline is divided into16 sections for scoring. The CAPT was completed at baseline and monthly during study participation.

    Total CAPT scores were calculated by adding the total score and dividing by 16. Score range is 1-5. Lower scores indicate less body dissatisfaction.

    Change in the CAPT score during the study was calculated using an estimate of change in score between week 0 and week 7 derived from the mixed effect model across all time points.


  • Body Image Software (BIS): Average Distortion [ Time Frame: monthly ] [ Designated as safety issue: No ]

    Body Image Software (BIS) - the subject adjusts a digital image of themselves on the computer using the direction to "adjust their image to how they see themselves right now", this determines their perception of their current image. Accuracy is measured by a smaller score between desired image and actual image.

    Change in the BIS Average Distortion score during the study was calculated using an estimate of change in score between week 0 and week 7 derived from the mixed effect model across all time points.

    There are no identifiable minimum/maximum values as there would be in a questionnaire scale. There are no subscales. The BIS program calculates the difference between their actual image and the size of the image they have adjusted the digital image to based on their perception of "how they see themselves right now"


  • Body Image Software (BIS): Average Desired Thinness [ Time Frame: monthly ] [ Designated as safety issue: No ]

    Body Image Software (BIS) - the subject adjusts a digital image of themselves on the computer to "their desired image". The BIS program calculates the difference between their actual image, and how much they have adjusted the image to represent their "desired image". Accuracy is measured by a smaller score between desired image and actual image.

    Change in BIS - Average Desired Thinness score was calculated using an estimate of change in score between week 0 and week 7 derived from the mixed effect model across all time points.

    There are no identifiable minimum/maximum values as there would be in a questionnaire scale. . There are no subscales.


  • Body Image Software (BIS) - Point of Subjective Equality (PSE) [ Time Frame: monthly ] [ Designated as safety issue: No ]

    Body Image Software (BIS) - the subject adjusts a digital image of themselves on the computer to their desired image, and also completes a task that determines their perception of their current image. Accuracy is measured by a smaller score between desired image and actual image.

    Change in BIS -PSE was calculated using an estimate of change in score between week 0 and week 7 derived from the mixed effect model across all time points.

    There are no identifiable minimum/maximum values as there would be in a questionnaire scale. Interpreting the PSE is how it compares to a PSE = 0, which is no distortion in body size.


  • Body Image Software (BIS) - Difference Limen (DL) [ Time Frame: monthly ] [ Designated as safety issue: No ]

    Body Image Software (BIS) - the subject adjusts a digital image of themselves on the computer to their desired image, and also completes a task that determines their perception of their current image. Accuracy is measured by a smaller score between desired image and actual image.

    Change in BIS-DL was calculated using an estimate of change in score between week 0 and week 7 derived from the mixed effect model across all time points.

    There are no identifiable minimum/maximum values as there would be in a questionnaire scale. There are no subscales. Interpreting the DL occurs by referencing it to DL= 0, which would reflect a total inability to detect size differences, which has never occurred in studies using the BIS program.



Secondary Outcome Measures:
  • Time to Reach 90% Ideal Body Weight (IBW) and Maintain for 1 Month, Stratified by >=80% at Start of Study [ Time Frame: weekly ] [ Designated as safety issue: No ]
    The mean survival time and its standard error were underestimated because the largest observation was censored and the estimation was restricted to the largest event time. These estimates were produced using Kaplan-Meier probabilities. This was measured weekly from 0-18 weeks.

  • Change in Ratings of Anxiety Symptoms on the Multidimensional Anxiety Scale for Children (MASC) [ Time Frame: monthly to study end point ] [ Designated as safety issue: No ]

    The Multidimensional Anxiety Scale for Children (MASC) is a self report measure completed by the subject that measures anxiety symptoms.

    Higher scores indicate greater anxiety. A score of over 50 is significant for anxiety

    Change in MASC scores was calculated using an estimate of change in score between week 0 and week 7 derived from the mixed effect model across all time points.


  • Change in Leptin Levels [ Time Frame: Week 0 and week 7 ] [ Designated as safety issue: Yes ]
    Leptin levels were measured by serum blood draws, results reports in nanograms / ml (ng/ml).

  • Change in Prolactin Levels [ Time Frame: week 0 and week 7 ] [ Designated as safety issue: Yes ]
    Prolactin serum blood levels, measured in nanograms / ml

  • Time to Reach 90% IBW and Maintain for 1 Month, Stratified by IBW <80% at Start of Study [ Time Frame: 0 - 18 weeks ] [ Designated as safety issue: No ]
    The mean survival time and its standard error were underestimated because the largest observation was censored and the estimation was restricted to the largest event time. These estimates were produced using Kaplan-Meier probabilities.


Enrollment: 41
Study Start Date: August 2004
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: placebo
double blind study of risperidone for anorexia nervosa. this is the subject group that receives placebo.
Drug: Placebo
Comparison of risperidone versus placebo for the treatment of symptoms related to anorexia nervosa.
Other Name: placebo - inactive pill
Active Comparator: risperidone
Study is double blind, placebo controlled. This is the subject group on active medication
Drug: Risperidone
risperidone titrated 0.5 to 4 mg over study enrollment. Mean Length of Phase 1 is currently 10 weeks.
Other Name: Risperdal

Detailed Description:
The lack of effective medications for the symptoms of anorexia nervosa (AN), combined with early promising findings in case reports (Risperidone and Olanzapine) and one open study of olanzapine have led to increased use of these medications for individuals with AN. This double-blind placebo controlled study of risperidone will attempt to determine if risperidone is effective in decreasing core symptoms of anorexia nervosa and decreasing the length of time required to reach and maintain at or about 90% Ideal body weight. The safety of risperidone in this population will also be examined through monitoring of Extrapyramidal Symptoms, Tardive Dyskinesia, Electrocardiograms's, Resting Energy Expenditure, liver enzymes and other blood chemistry. Other possible variables which may mediate the recovery process or be impacted by risperidone,such as leptin and anxiety symptoms are also being measured.
  Eligibility

Ages Eligible for Study:   12 Years to 21 Years   (Child, Adult)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Primary Diagnosis of Anorexia Nervosa
  • Female, age 12-21
  • Active in a level of care for AN at The Children's Hospital, Denver
  • As long as there is a primary dx of AN, co-morbid diagnoses may be included.
  • If taking an antidepressant, must be on a stable dose for 3 weeks prior to entering the study, and dose of antidepressant may not be changed during Phase 1 of the study.
  • If choosing to discontinue antidepressant medication, must be off the medication for 3 weeks prior to beginning the study.
  • If sexually active, must use birth control during the study and have a monthly pregnancy test.

Exclusion Criteria:

  • Previous enrollment in this study on a prior admission
  • Previous allergic reaction to risperidone or other atypical neuroleptic
  • Positive pregnancy test
  • Neurologic disorder other than benign essential tremor
  • Taking a psychotropic medication other than antidepressant and discontinuing the medication is not recommended.
  • Active hepatic or renal disease
  • Wards of the state
  • Males
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00140426

Locations
United States, Colorado
The Children's Hospital
Denver, Colorado, United States, 80218
Sponsors and Collaborators
University of Colorado, Denver
Janssen Pharmaceuticals
National Center for Research Resources (NCRR)
Investigators
Principal Investigator: Jennifer O Hagman, MD University of Colorado, Health Sciences Center and The Children's Hospital, Denver
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT00140426     History of Changes
Other Study ID Numbers: 03-0673  5M01RR000069-45 
Study First Received: August 31, 2005
Results First Received: June 8, 2015
Last Updated: December 29, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by University of Colorado, Denver:
Anorexia Nervosa
Risperidone
Atypical Neuroleptics
Dopamine
Leptin
Body Image
Adolescents

Additional relevant MeSH terms:
Anorexia
Anorexia Nervosa
Signs and Symptoms, Digestive
Signs and Symptoms
Feeding and Eating Disorders
Mental Disorders
Risperidone
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents

ClinicalTrials.gov processed this record on September 28, 2016