Trial Outcomes & Findings for Early Intervention With Fluoxetine in Autism (NCT NCT00183339)

Last Updated: 2014-03-26

Results Overview

In order for a larger trial with similar design to be feasible a number of factors needed to be examined. The first was whether families would enroll very young children with ASD into a year long blinded medication study. To determine this we examined the average number of months to randomize 1 participant per site. We calculated this (as total # months required for recruitment\* 2sites ) /\[ # participants randomized \] and compared it to the typical # of months required to recruit an older child with ASD for a double-blind 12 week placebo controlled medication study, which is typically about 1.2 months at each of the sites involved in the study.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

18 participants

Primary outcome timeframe

19 months

Results posted on

2014-03-26

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Participants who received placebo solution between .5ml and 5.0ml	Fluoxetine Participants who received liquid fluoxetine 2-20 mg (of 4mg/1ml solution) in AM using a flexible dose strategy and planned 36 week titration schedule
Overall Study STARTED	10	8
Overall Study COMPLETED	4	4
Overall Study NOT COMPLETED	6	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Early Intervention With Fluoxetine in Autism

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=10 Participants Participants will take the placebo	Fluoxetine n=8 Participants Participants will take liquid fluoxetine 2-20 mg	Total n=18 Participants Total of all reporting groups
Age, Categorical <=18 years	10 Participants n=5 Participants	8 Participants n=7 Participants	18 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	44.0 months STANDARD_DEVIATION 6.6 • n=5 Participants	42.6 months STANDARD_DEVIATION 8.1 • n=7 Participants	43.4 months STANDARD_DEVIATION 7.4 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	8 Participants n=7 Participants	18 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	10 participants n=5 Participants	8 participants n=7 Participants	18 participants n=5 Participants

PRIMARY outcome

Timeframe: 19 months

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Participants will take the placebo	Fluoxetine n=8 Participants Participants will take liquid fluoxetine 2-20 mg
Rate of Recruitment	2.1 months/participant at 1 site	2.1 months/participant at 1 site

SECONDARY outcome

Timeframe: Measured at Month 12

The percentage of participants who discontinued treatment prior to completion of the 12 month study

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Participants will take the placebo	Fluoxetine n=8 Participants Participants will take liquid fluoxetine 2-20 mg
Rate of Attrition	60 percent of group that discontinued early	50 percent of group that discontinued early

SECONDARY outcome

Timeframe: 12 months

This is a caregiver completed measure that assesses the extent to which the caregiver feels care of the participant influences the caregiver's and other family members' emotional states and/or activities. There are a total of 22 items rated from 1 - not at all to 5 - very much (with one item reverse scored). Total score is the sum of all the items (with one item reverse scored). There are three subscales objective strain -12 items, internalized subjective strain 6 items, externalized subjective 4 items. The total score can range from a minimum of 0 - no strain at all, to 110 all items rated as very much.

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Participants will take the placebo	Fluoxetine n=8 Participants Participants will take liquid fluoxetine 2-20 mg
Change From Baseline to 12 Months in Total Score on Caregiver Strain Questionnaire	0.8 units on a scale Standard Deviation 2.5	-1.86 units on a scale Standard Deviation 2.3

SECONDARY outcome

Timeframe: 12 months

The Aberrant Behavior Checklist (ABC) is a caregiver completed rating scale that assesses problem behaviors frequently seen in individuals with developmental disabilities. There are a total of 58 items on 5 subscales that are rated from 0 - not at all a problem to 3 - problem is severe in degree. The ABC-I consists of 15 items that reflect mood swings, self-injury and aggression. The subscale score is the sum of the score on each of the 15 items. The minimum score on the ABC-I is 0 and the maximum score is 45. Higher scores reflect more severe behavioral problems. A score \> or = to 18 is generally considered clinically significant.

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Participants will take the placebo	Fluoxetine n=8 Participants Participants will take liquid fluoxetine 2-20 mg
Change From Baseline to Month 12 in Aberrant Behavior Checklist Irritability Subscale Score (ABC-I)	-0.70 units on a scale Standard Deviation 2.9	-8.50 units on a scale Standard Deviation 10.6

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Fluoxetine

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=10 participants at risk participants who were treated with flexible dose placebo solution	Fluoxetine n=8 participants at risk participants who were treated with flexible dose fluoxetine solution, 2-20mg per day
Gastrointestinal disorders Severe Diarrhea	10.0% 1/10 • Number of events 1 • 12 months (The course of treatment for each participant in the trial)	0.00% 0/8 • 12 months (The course of treatment for each participant in the trial)

Other adverse events

Additional Information

Linmarie Sikich, MD

University of North Carolina

Phone: 919 966 8653

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Placebo n=10 participants at risk participants who were treated with flexible dose placebo solution	Fluoxetine n=8 participants at risk participants who were treated with flexible dose fluoxetine solution, 2-20mg per day
Blood and lymphatic system disorders Nosebleed	20.0% 2/10 • Number of events 2 • 12 months (The course of treatment for each participant in the trial)	25.0% 2/8 • Number of events 2 • 12 months (The course of treatment for each participant in the trial)
Blood and lymphatic system disorders bruise	0.00% 0/10 • 12 months (The course of treatment for each participant in the trial)	12.5% 1/8 • Number of events 1 • 12 months (The course of treatment for each participant in the trial)
Infections and infestations Cold/Flu/other systemic infection	70.0% 7/10 • Number of events 7 • 12 months (The course of treatment for each participant in the trial)	75.0% 6/8 • Number of events 6 • 12 months (The course of treatment for each participant in the trial)
Ear and labyrinth disorders Earache	30.0% 3/10 • Number of events 3 • 12 months (The course of treatment for each participant in the trial)	37.5% 3/8 • Number of events 3 • 12 months (The course of treatment for each participant in the trial)
Eye disorders other eye disorders	0.00% 0/10 • 12 months (The course of treatment for each participant in the trial)	37.5% 3/8 • Number of events 3 • 12 months (The course of treatment for each participant in the trial)
Gastrointestinal disorders gastroenteritis	60.0% 6/10 • Number of events 6 • 12 months (The course of treatment for each participant in the trial)	75.0% 6/8 • Number of events 6 • 12 months (The course of treatment for each participant in the trial)
Immune system disorders allergies	30.0% 3/10 • Number of events 3 • 12 months (The course of treatment for each participant in the trial)	50.0% 4/8 • Number of events 4 • 12 months (The course of treatment for each participant in the trial)
Injury, poisoning and procedural complications intentional injury	10.0% 1/10 • Number of events 1 • 12 months (The course of treatment for each participant in the trial)	12.5% 1/8 • Number of events 1 • 12 months (The course of treatment for each participant in the trial)
Infections and infestations Local Infection	10.0% 1/10 • Number of events 1 • 12 months (The course of treatment for each participant in the trial)	0.00% 0/8 • 12 months (The course of treatment for each participant in the trial)
Metabolism and nutrition disorders weight increased	0.00% 0/10 • 12 months (The course of treatment for each participant in the trial)	25.0% 2/8 • Number of events 2 • 12 months (The course of treatment for each participant in the trial)
Psychiatric disorders aggression	40.0% 4/10 • Number of events 4 • 12 months (The course of treatment for each participant in the trial)	62.5% 5/8 • Number of events 5 • 12 months (The course of treatment for each participant in the trial)
Infections and infestations Other infection	20.0% 2/10 • Number of events 2 • 12 months (The course of treatment for each participant in the trial)	12.5% 1/8 • Number of events 1 • 12 months (The course of treatment for each participant in the trial)
Renal and urinary disorders enuresis	20.0% 2/10 • Number of events 2 • 12 months (The course of treatment for each participant in the trial)	62.5% 5/8 • Number of events 5 • 12 months (The course of treatment for each participant in the trial)
Respiratory, thoracic and mediastinal disorders cough	30.0% 3/10 • Number of events 3 • 12 months (The course of treatment for each participant in the trial)	50.0% 4/8 • Number of events 4 • 12 months (The course of treatment for each participant in the trial)
General disorders Sensory Sensitivity	10.0% 1/10 • Number of events 1 • 12 months (The course of treatment for each participant in the trial)	12.5% 1/8 • Number of events 1 • 12 months (The course of treatment for each participant in the trial)
General disorders Sexual	0.00% 0/10 • 12 months (The course of treatment for each participant in the trial)	12.5% 1/8 • Number of events 1 • 12 months (The course of treatment for each participant in the trial)
Skin and subcutaneous tissue disorders rash	50.0% 5/10 • Number of events 5 • 12 months (The course of treatment for each participant in the trial)	25.0% 2/8 • Number of events 2 • 12 months (The course of treatment for each participant in the trial)
General disorders insomnia	50.0% 5/10 • Number of events 5 • 12 months (The course of treatment for each participant in the trial)	62.5% 5/8 • Number of events 5 • 12 months (The course of treatment for each participant in the trial)
Nervous system disorders irritability	40.0% 4/10 • Number of events 4 • 12 months (The course of treatment for each participant in the trial)	37.5% 3/8 • Number of events 3 • 12 months (The course of treatment for each participant in the trial)
Psychiatric disorders mood lability	30.0% 3/10 • Number of events 3 • 12 months (The course of treatment for each participant in the trial)	0.00% 0/8 • 12 months (The course of treatment for each participant in the trial)