Condition category
Mental and Behavioural Disorders
Date applied
20/03/2010
Date assigned
25/03/2010
Last edited
16/08/2011
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Mark Geier

ORCID ID

Contact details

14 Redgate Ct
Silver Spring
20905
United States of America

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

Autism-Carnitine Study#1

Study information

Scientific title

A Prospective Double-Blind, Randomized Clinical Trial of Levocarnitine to Treat Autism Spectrum Disorders

Acronym

Study hypothesis

The hypothesis tested in the present study was that blood carnitine levels in patients diagnosed with an ASD have a significant impact on behaviour, cognition, socialization, and health/physical traits associated with an ASD diagnosis. The present prospective, double-blind, placebo controlled trial evaluated whether a standardized treatment regimen of liquid L-carnitine administered to patients diagnosed with an autism spectrum disorder (ASD) on a daily basis for 3-months would result in improved behaviour, cognition, socialization, and health/physical traits associated with an ASD diagnosis.

Ethics approval

Liberty IRB, Inc. (Deland, Florida) approved on the 25th of September 2008 (ref: 08.09.0016)

Study design

Randomised double blind placebo controlled study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details below to request a patient information sheet

Condition

Autism Spectrum Disorder (ASD)

Intervention

L-carnitine supplied in a liquid preparation by the Wellness Pharmacy (Birmingham, AL, USA) using a specific formula containing: 100 mg L-Carntine/mL with the inactive ingredients of methylcellulose, stevioside (stevia), tangerine flavour, and preserved water (containing methylparaben and propylparaben).
Placebos identical in appearance and taste to the active preparation, containing a 1% methylcellulose suspension with the inactive ingredients of stevioside (stevia), tangerine flavour, and preserved water (containing methylparaben and propylparaben).
A dose of 50 mg L-carnitine per Kg bodyweight per day (half the total dose administered in the morning and half the total dose administered in the evening) will be utilized in the present study with dosing calculated based on each participant’s intake weight.
The dosing regimen of the liquid preparation will be identical in both the L-carnitine and placebo groups, so that each study subject received a total of 0.5 mL per Kg of bodyweight per day (administered as 0.25 mL per Kg of bodyweight in the morning and 0.25 mL per Kg of bodyweight in the evening).
Study subject-specific dosing instructions will be placed on each liquid preparation provided to study subjects.

Intervention type

Drug

Phase

Not Specified

Drug names

L-carnitine

Primary outcome measures

1. Childhood Autism Rating Scale (CARS)
Study participants will be evaluated using a CARS test conducted only by a single study investigator who observed the subjects and interviewed the parent(s), and was unaware as to the treatment status of the subject. The CARS test is a 15-item behavioural rating scale developed to identify autism as well as to quantitatively describe the severity of the disorder. The CARS test is a well-established measure of autism severity. The internal consistency reliability alpha coefficient is 0.94; the inter-rater reliability correlation coefficient is 0.71; and the test-retest correlation coefficient is 0.88. CARS scores have high criterion-related validity when compared to clinical ratings during the same diagnostic sessions, with a significant correlation of 0.84.
2. Autism Treatment Evaluation Checklist (ATEC)
Each study subject will be evaluated by their parents using an ATEC form. Parents will be unaware as to the treatment status of their child. The ATEC, designed by the Autism Research Institute (San Diego, CA, USA), is a one-page form. It consists of four subtests designed to measure the effects of treatment in persons with autism. The items are: (1) Speech/Language/Communication (14 items); (2) Sociability (20 items); (3) Sensory/Cognitive Awareness (18 items); and (4) Health/Physical/Behavior (25 items). The internal consistency reliability of the measure is high (0.94 for the Total score). The ATEC has been successfully used to measure treatment effects in autism.
3. Clinical Global Impression (CGI)
An overall CGI score will be collected by a single study investigator unaware of the treatment status of the study subject using a 3 point scoring system defined as follows: subject improved = 1, subject the same = 2, and subject worse = 3.
4. Hand Muscle Testing
Each subject will have their hand muscle strength tested using a pneumatic, adjustable squeeze pinch-gauge/dynamometer (Baseline Evaluation Instruments; White Plains, NY, USA) by a study investigator unaware of the treatment status of the subject. This instrument is a reliable and valid method for obtaining muscle force or torque measurements in children. Subjects will be tested using the smallest hand grasp bulb, and were given as many tries as needed to register their maximum grasp reading measured in kilopascals (kPa) for each hand. Special emphasis will be placed to ensure that the subject positioned the bulb in the palm of the hand and held the bulb in space to ensure that pressure was not applied by the study subject against a fixed surface. In addition, each study subject will be strongly encouraged by a study investigator to give maximum effort.

Secondary outcome measures

1. Treatment Adherence Measure (TAM) Form
A treatment adherence measure (TAM) form will be completed by the parents of each study subject. Parents will be unaware as to the treatment status of their child. The TAM is a ten-item self-report on treatment adherence that asks specific questions regarding the dose and frequency of use. The TAM was used to calculate the level of adherence to the treatment. It is a Morisky-type self-report adherence measure, designed to measure treatment adherence. Morisky-type adherence measures have been used widely, demonstrating good reliability as a self-report measure.
2. Side effects
2.1. Frequency and Intensity of Side Effect Rating (FISER)
2.2. Global Rating of Side Effect Burden (GRSEB)
2.3. Patient Report of Incidence of Side Effects (PRISE)
The FISER/GRSEB/PRISE forms will be completed by the parents of study subjects that will be unaware of the treatment status of their children. The FISER/GRSEB/PRISE forms include global measures, each using a 7-point Likert-type scale rated 0-6, with one rating anchored for frequency, another rating the intensity of side effects encountered in the prior week that the study subject parents believed were due to the treatment, and the third asking the parents of study subjects to estimate the overall burden or degree of interference in day-to-day activities and function due to the side effects attributable specifically to the treatment. Frequency of side effects is rated as a percent time present: 0 = no side effects; 1 = present 10% of the time; 2 = 25% of the time; 3 = 50% of the time; 4 = 75%; 5 = 90%; and 6 = present all of the time. Intensity of side effects ranges from 0 = no side effects to 6 = intolerable side-effects. Impairment due to side effects ranges from 0 = no side effects to 6 = unable to function at all due to side-effects. The PRISE lists a variety of possible side effects from which to choose and a scale to rate the specific side effect. The measure also has a place to list any side effects not previously listed.
3. Lab testing
Study subjects will have lab testing collected at a Laboratory Corporation of American (LabCorp) draw station in the morning following an overnight fast. The lab will not be made aware of the treatment status of the study subjects. The procedures for collection and analysis were defined by LabCorp standard protocols (CLIA-approved). The following blood tests will be collected and evaluated on each study subject, including:
3.1. Whole blood white blood cell count (WBC)
3.2. Whole blood red blood cell count (RBC)
3.3. Whole blood platelet count
3.4. Serum creatinine
3.5. Serum blood urine nitrogen (BUN)
3.6. Serum alkaline phosphatase
3.7. Serum aspartate aminotransferase (AST/SGOT)
3.8. Serum alanine aminotransferase (ALT/SGPT)
3.9. Serum glucose
3.10. Serum carnitine (total and free)

Overall trial start date

01/01/2009

Overall trial end date

31/12/2009

Reason abandoned

Eligibility

Participant inclusion criteria

1. Subjects diagnosed with an ASD
2. Aged from 3 to 10 yrs-old (males and females)
3. Study subject bodyweights between 13.2 Kg to 40.4 Kg

Participant type

Patient

Age group

Child

Gender

Both

Target number of participants

30

Participant exclusion criteria

1. No study subject previously received carnitine-based therapy or previous methionine or lysine supplementation
2. No study subject had any change in therapy or treatment (including medications) within 1 month prior to the study

Recruitment start date

01/01/2009

Recruitment end date

31/12/2009

Locations

Countries of recruitment

United States of America

Trial participating centre

14 Redgate Ct
Silver Spring
20905
United States of America

Sponsor information

Organisation

Autism Research Institute (USA)

Sponsor details

4182 Adams Avenue
San Diego
92116
United States of America

Sponsor type

Research organisation

Website

http://www.autism.com/index.asp

Funders

Funder type

Research organisation

Funder name

Autism Research Institute (USA)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

CoMeD, Inc. (USA)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

The Institute of Chronic Illnesses, Inc. (USA)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes