Trial Outcomes & Findings for A Double-blind, Placebo Controlled Trial of Risperidone for the Treatment of Anorexia Nervosa (NCT NCT00140426)

NCT ID: NCT00140426

Last Updated: 2016-02-02

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 41 participants
• Primary outcome timeframe: month
• Results posted on: 2016-02-02

Participant Flow

Participant milestones

Measure	Placebo double blind study of risperidone for anorexia nervosa. this is the subject group that receives placebo. Risperidone or placebo: risperidone titrated 0.5 to 4 mg over study enrollment. Mean Length of Phase 1 is currently 10 weeks.	Risperidone Study is double blind, placebo controlled. This is the subject group on active medication Risperidone: Comparison of risperidone versus placebo for the treatment of symptoms related to anorexia nervosa. Titration of study medication from 0.5 to 4 mg based on weight gain to target IBW.
Overall Study STARTED	22	19
Overall Study COMPLETED	22	16
Overall Study NOT COMPLETED	0	3

Reasons for withdrawal

Measure	Placebo double blind study of risperidone for anorexia nervosa. this is the subject group that receives placebo. Risperidone or placebo: risperidone titrated 0.5 to 4 mg over study enrollment. Mean Length of Phase 1 is currently 10 weeks.	Risperidone Study is double blind, placebo controlled. This is the subject group on active medication Risperidone: Comparison of risperidone versus placebo for the treatment of symptoms related to anorexia nervosa. Titration of study medication from 0.5 to 4 mg based on weight gain to target IBW.
Overall Study Withdrawal by Subject	0	3

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Placebo n=22 Participants double blind study of risperidone for anorexia nervosa. this is the subject group that receives placebo. Risperidone or placebo: risperidone titrated 0.5 to 4 mg over study enrollment. Mean Length of Phase 1 is currently 10 weeks.	Risperidone n=19 Participants Study is double blind, placebo controlled. This is the subject group on active medication Risperidone: Comparison of risperidone versus placebo for the treatment of symptoms related to anorexia nervosa. Titration of study medication from 0.5 to 4 mg based on weight gain to target IBW.	Total n=41 Participants Total of all reporting groups
Age, Categorical <=18 years	19 Participants n=5 Participants	13 Participants n=7 Participants	32 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	15.8 years STANDARD_DEVIATION 2.3 • n=5 Participants	16.2 years STANDARD_DEVIATION 2.5 • n=7 Participants	15.98 years STANDARD_DEVIATION 2.35 • n=5 Participants
Sex: Female, Male Female	22 Participants n=5 Participants	19 Participants n=7 Participants	41 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	22 participants n=5 Participants	19 participants n=7 Participants	41 participants n=5 Participants

PRIMARY outcome

Timeframe: month

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.

Outcome measures

Measure	Placebo n=22 Participants double blind study of risperidone for anorexia nervosa. this is the subject group that receives placebo. Risperidone or placebo: risperidone titrated 0.5 to 4 mg over study enrollment. Mean Length of Phase 1 is currently 10 weeks.	Risperidone n=16 Participants Study is double blind, placebo controlled. This is the subject group on active medication Risperidone: Comparison of risperidone versus placebo for the treatment of symptoms related to anorexia nervosa. Titration of study medication from 0.5 to 4 mg based on weight gain to target IBW.
Change in Eating Disorder Inventory-2 Drive for Thinness Subscale (DT)	1.36 units on a scale Standard Deviation 5.09	3.93 units on a scale Standard Deviation 6.95

PRIMARY outcome

Timeframe: monthly

Population: 1 risperidone subject was missing data for BD at this data point.

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.

Outcome measures

Measure	Placebo n=22 Participants double blind study of risperidone for anorexia nervosa. this is the subject group that receives placebo. Risperidone or placebo: risperidone titrated 0.5 to 4 mg over study enrollment. Mean Length of Phase 1 is currently 10 weeks.	Risperidone n=15 Participants Study is double blind, placebo controlled. This is the subject group on active medication Risperidone: Comparison of risperidone versus placebo for the treatment of symptoms related to anorexia nervosa. Titration of study medication from 0.5 to 4 mg based on weight gain to target IBW.
Change in Eating Disorder Inventory (EDI)-2 Score for Body Dissatisfaction (BD)	0.82 units on a scale Standard Deviation 5.96	2.67 units on a scale Standard Deviation 7.93

PRIMARY outcome

Timeframe: weekly up to study endpoint: reaching target weight and maintaining for 1 month

Population: 2 patients in the placebo group were treated as inpatients and had no EOE data.

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.

Outcome measures

Measure	Placebo n=20 Participants double blind study of risperidone for anorexia nervosa. this is the subject group that receives placebo. Risperidone or placebo: risperidone titrated 0.5 to 4 mg over study enrollment. Mean Length of Phase 1 is currently 10 weeks.	Risperidone n=16 Participants Study is double blind, placebo controlled. This is the subject group on active medication Risperidone: Comparison of risperidone versus placebo for the treatment of symptoms related to anorexia nervosa. Titration of study medication from 0.5 to 4 mg based on weight gain to target IBW.
Hazard Ratio for Time to Reaching Ease Of Eating Level 3 From Start of Study (Normal Eating Behavior)	0.85 hazard ratio Interval 0.41 to 1.74	1 hazard ratio Interval 1.0 to 1.0

PRIMARY outcome

Timeframe: monthly

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.

Outcome measures

Measure	Placebo n=22 Participants double blind study of risperidone for anorexia nervosa. this is the subject group that receives placebo. Risperidone or placebo: risperidone titrated 0.5 to 4 mg over study enrollment. Mean Length of Phase 1 is currently 10 weeks.	Risperidone n=18 Participants Study is double blind, placebo controlled. This is the subject group on active medication Risperidone: Comparison of risperidone versus placebo for the treatment of symptoms related to anorexia nervosa. Titration of study medication from 0.5 to 4 mg based on weight gain to target IBW.
Color A Person Test (CAPT)	0.03 units on a scale Standard Deviation 0.75	0.22 units on a scale Standard Deviation 0.79

PRIMARY outcome

Timeframe: monthly

Population: Change from baseline to end of study was compared between arms. Some patients did not complete this outcome measurement.

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"

Outcome measures

Measure	Placebo n=21 Participants double blind study of risperidone for anorexia nervosa. this is the subject group that receives placebo. Risperidone or placebo: risperidone titrated 0.5 to 4 mg over study enrollment. Mean Length of Phase 1 is currently 10 weeks.	Risperidone n=16 Participants Study is double blind, placebo controlled. This is the subject group on active medication Risperidone: Comparison of risperidone versus placebo for the treatment of symptoms related to anorexia nervosa. Titration of study medication from 0.5 to 4 mg based on weight gain to target IBW.
Body Image Software (BIS): Average Distortion	-0.22 units on a scale Standard Deviation 8.75	1.40 units on a scale Standard Deviation 8.36

PRIMARY outcome

Timeframe: monthly

Population: Many patients did not complete this outcome measurement. Change from baseline to end of study were compared between arms.

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.

Outcome measures

Measure	Placebo n=10 Participants double blind study of risperidone for anorexia nervosa. this is the subject group that receives placebo. Risperidone or placebo: risperidone titrated 0.5 to 4 mg over study enrollment. Mean Length of Phase 1 is currently 10 weeks.	Risperidone n=7 Participants Study is double blind, placebo controlled. This is the subject group on active medication Risperidone: Comparison of risperidone versus placebo for the treatment of symptoms related to anorexia nervosa. Titration of study medication from 0.5 to 4 mg based on weight gain to target IBW.
Body Image Software (BIS): Average Desired Thinness	1.88 units on a scale Standard Deviation 9.24	-1.42 units on a scale Standard Deviation 10.31

PRIMARY outcome

Timeframe: monthly

Population: Change from baseline to end of study was compared between arms. Some patients did not complete this outcome measurement.

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.

Outcome measures

Measure	Placebo n=19 Participants double blind study of risperidone for anorexia nervosa. this is the subject group that receives placebo. Risperidone or placebo: risperidone titrated 0.5 to 4 mg over study enrollment. Mean Length of Phase 1 is currently 10 weeks.	Risperidone n=16 Participants Study is double blind, placebo controlled. This is the subject group on active medication Risperidone: Comparison of risperidone versus placebo for the treatment of symptoms related to anorexia nervosa. Titration of study medication from 0.5 to 4 mg based on weight gain to target IBW.
Body Image Software (BIS) - Point of Subjective Equality (PSE)	-0.32 units on a scale Standard Deviation 5.81	-2.18 units on a scale Standard Deviation 7.92

PRIMARY outcome

Timeframe: monthly

Population: Change from baseline to end of study was compared between arms. Some patients did not complete this outcome measurement.

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.

Outcome measures

Measure	Placebo n=19 Participants double blind study of risperidone for anorexia nervosa. this is the subject group that receives placebo. Risperidone or placebo: risperidone titrated 0.5 to 4 mg over study enrollment. Mean Length of Phase 1 is currently 10 weeks.	Risperidone n=16 Participants Study is double blind, placebo controlled. This is the subject group on active medication Risperidone: Comparison of risperidone versus placebo for the treatment of symptoms related to anorexia nervosa. Titration of study medication from 0.5 to 4 mg based on weight gain to target IBW.
Body Image Software (BIS) - Difference Limen (DL)	-0.19 units on a scale Standard Deviation 1.10	-1.16 units on a scale Standard Deviation 2.18

SECONDARY outcome

Timeframe: weekly

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.

Outcome measures

Measure	Placebo n=10 Participants double blind study of risperidone for anorexia nervosa. this is the subject group that receives placebo. Risperidone or placebo: risperidone titrated 0.5 to 4 mg over study enrollment. Mean Length of Phase 1 is currently 10 weeks.	Risperidone n=6 Participants Study is double blind, placebo controlled. This is the subject group on active medication Risperidone: Comparison of risperidone versus placebo for the treatment of symptoms related to anorexia nervosa. Titration of study medication from 0.5 to 4 mg based on weight gain to target IBW.
Time to Reach 90% Ideal Body Weight (IBW) and Maintain for 1 Month, Stratified by >=80% at Start of Study	10.7 weeks Standard Error 1.6	8.1 weeks Standard Error 0.2

SECONDARY outcome

Timeframe: monthly to study end point

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.

Outcome measures

Measure	Placebo n=18 Participants double blind study of risperidone for anorexia nervosa. this is the subject group that receives placebo. Risperidone or placebo: risperidone titrated 0.5 to 4 mg over study enrollment. Mean Length of Phase 1 is currently 10 weeks.	Risperidone n=15 Participants Study is double blind, placebo controlled. This is the subject group on active medication Risperidone: Comparison of risperidone versus placebo for the treatment of symptoms related to anorexia nervosa. Titration of study medication from 0.5 to 4 mg based on weight gain to target IBW.
Change in Ratings of Anxiety Symptoms on the Multidimensional Anxiety Scale for Children (MASC)	7.41 units on a scale Standard Deviation 7.87	7.87 units on a scale Standard Deviation 11.19

SECONDARY outcome

Timeframe: Week 0 and week 7

Leptin levels were measured by serum blood draws, results reports in nanograms / ml (ng/ml).

Outcome measures

Measure	Placebo n=19 Participants double blind study of risperidone for anorexia nervosa. this is the subject group that receives placebo. Risperidone or placebo: risperidone titrated 0.5 to 4 mg over study enrollment. Mean Length of Phase 1 is currently 10 weeks.	Risperidone n=12 Participants Study is double blind, placebo controlled. This is the subject group on active medication Risperidone: Comparison of risperidone versus placebo for the treatment of symptoms related to anorexia nervosa. Titration of study medication from 0.5 to 4 mg based on weight gain to target IBW.
Change in Leptin Levels	0.88 ng/ml Standard Deviation 4.13	3.27 ng/ml Standard Deviation 3.04

SECONDARY outcome

Timeframe: week 0 and week 7

Prolactin serum blood levels, measured in nanograms / ml

Outcome measures

Measure	Placebo n=19 Participants double blind study of risperidone for anorexia nervosa. this is the subject group that receives placebo. Risperidone or placebo: risperidone titrated 0.5 to 4 mg over study enrollment. Mean Length of Phase 1 is currently 10 weeks.	Risperidone n=12 Participants Study is double blind, placebo controlled. This is the subject group on active medication Risperidone: Comparison of risperidone versus placebo for the treatment of symptoms related to anorexia nervosa. Titration of study medication from 0.5 to 4 mg based on weight gain to target IBW.
Change in Prolactin Levels	-5.18 ng/ml Standard Deviation 5.89	38.27 ng/ml Standard Deviation 33.05

SECONDARY outcome

Timeframe: 0 - 18 weeks

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.

Outcome measures

Measure	Placebo n=12 Participants double blind study of risperidone for anorexia nervosa. this is the subject group that receives placebo. Risperidone or placebo: risperidone titrated 0.5 to 4 mg over study enrollment. Mean Length of Phase 1 is currently 10 weeks.	Risperidone n=12 Participants Study is double blind, placebo controlled. This is the subject group on active medication Risperidone: Comparison of risperidone versus placebo for the treatment of symptoms related to anorexia nervosa. Titration of study medication from 0.5 to 4 mg based on weight gain to target IBW.
Time to Reach 90% IBW and Maintain for 1 Month, Stratified by IBW <80% at Start of Study	10.1 weeks Standard Error 0.4	12.9 weeks Standard Error 1.3

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Risperidone

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Placebo n=22 participants at risk double blind study of risperidone for anorexia nervosa. this is the subject group that receives placebo. Risperidone or placebo: risperidone titrated 0.5 to 4 mg over study enrollment. Mean Length of Phase 1 is currently 10 weeks.	Risperidone n=18 participants at risk Study is double blind, placebo controlled. This is the subject group on active medication Risperidone: Comparison of risperidone versus placebo for the treatment of symptoms related to anorexia nervosa. Titration of study medication from 0.5 to 4 mg based on weight gain to target IBW.
Nervous system disorders Fatigue	36.4% 8/22 • Number of events 22 • While patients were on the study medication (placebo or risperidone)	61.1% 11/18 • Number of events 39 • While patients were on the study medication (placebo or risperidone)
Nervous system disorders dizziness	18.2% 4/22 • Number of events 4 • While patients were on the study medication (placebo or risperidone)	22.2% 4/18 • Number of events 15 • While patients were on the study medication (placebo or risperidone)
Gastrointestinal disorders gastrointestinal complaints	59.1% 13/22 • Number of events 53 • While patients were on the study medication (placebo or risperidone)	38.9% 7/18 • Number of events 35 • While patients were on the study medication (placebo or risperidone)
Nervous system disorders headache	36.4% 8/22 • Number of events 8 • While patients were on the study medication (placebo or risperidone)	22.2% 4/18 • Number of events 5 • While patients were on the study medication (placebo or risperidone)
Psychiatric disorders Depression	0.00% 0/22 • While patients were on the study medication (placebo or risperidone)	11.1% 2/18 • Number of events 2 • While patients were on the study medication (placebo or risperidone)
Psychiatric disorders Anxiety	13.6% 3/22 • Number of events 6 • While patients were on the study medication (placebo or risperidone)	5.6% 1/18 • Number of events 1 • While patients were on the study medication (placebo or risperidone)
Nervous system disorders insomnia	9.1% 2/22 • Number of events 4 • While patients were on the study medication (placebo or risperidone)	0.00% 0/18 • While patients were on the study medication (placebo or risperidone)
Musculoskeletal and connective tissue disorders Extrapyramidal symptoms (EPS)	36.4% 8/22 • Number of events 46 • While patients were on the study medication (placebo or risperidone)	44.4% 8/18 • Number of events 19 • While patients were on the study medication (placebo or risperidone)
Nervous system disorders Tardive dyskinesia	4.5% 1/22 • Number of events 2 • While patients were on the study medication (placebo or risperidone)	33.3% 6/18 • Number of events 14 • While patients were on the study medication (placebo or risperidone)

Additional Information

Jennifer Hagman MD

University of Colorado School of Medicine, Childrens Hospital Colorado

Phone: 720-777-2539

Email: jennifer.hagman@childrenscolorado.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place