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Does Clinical Treatment of Mitochondrial Dysfunction Impact Autism Spectrum Disorder (ASD)? (MitoASD)

Primary Purpose

Autism Spectrum Disorders, Mitochondrial Diseases

Status

Unknown status

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Mitochondrial Cocktail

About this trial

This is an interventional treatment trial for Autism Spectrum Disorders

Eligibility Criteria

3 Years - 12 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subject/legal representative is considered reliable and capable of adhering to the protocol (e.g., able to understand and complete diaries), visit schedule, and medication intake according to the judgment of the investigator.
.
Subject has a formal diagnosis of autistic spectrum disorders (ASD). the ASD diagnosis will satisfy the DSM- V criteria for ASD, and will be broad-spectrum including both severe and milder cases.
All subjects will have either suspected mitochondrial dysfunction as assessed by clinical evaluation, mitochondrial dysfunction as defined by the presence of significant abnormalities in their buccal mitochondrial respiratory complex activities (i.e., with either respiratory complex I or complex IV deficiencies) or have significantly aberrant specific activity ratios. Subjects with significant deficiencies in either muscle or skin fibroblast respiratory activities will also be included in those cases if buccal mitochondrial respiratory enzyme activity testing has not been performed.

Exclusion Criteria:

Subject has any medical or psychiatric condition that, in the opinion of the investigator, could jeopardize or would compromise the subject's ability to participate in this study.
Subject has a medical condition that could be expected in the opinion of the investigator to interfere with drug absorption, distribution, metabolism, or excretion.
Subject is on a ketogenic or other specialized diet. If the subject was on a specialized diet in the past, they must be off the diet for ≥2 months prior to the Baseline Period.
Subject has an acute or sub-acutely progressive central nervous system disease.
Subject has major brain deformation or severe cognitive dysfunction.
Subjects with epilepsy needing to take anti-seizure medications will be excluded.

Sites / Locations

St. Christopher's Hospital for ChildrenRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Mitochondrial Cocktail

Arm Description

The precise content of the Mitochondrial Cocktail will be: ubiquinol (liquid form, 150 mg/kg subject weight/day carnitine, 50 mg/kg subject weight/day alpha-lipoic acid, 100 mg/ day

Outcomes

Primary Outcome Measures

Change in features of Autistic behavior phenotype assessed using the Social Responsiveness Scale (SRS)

Change in Executive Function assessed using the Behavior Rating Inventory of Executive Function (BRIEF)

Secondary Outcome Measures

Changes in mitochondrial enzyme specific activities biochemically evaluated using buccal swab analysis

Change in buccal oxidative stress markers and mitochondrial DNA (mtDNA) damage

In buccal extracts, aconitase activity levels and mtDNA levels and integrity will be quantitatively evaluated at 0,3 and 6 months.

Full Information

NCT ID

NCT02348125

First Posted

December 22, 2014

Last Updated

April 12, 2017

Sponsor

Drexel University

1. Study Identification

Unique Protocol Identification Number

NCT02348125

Brief Title

Does Clinical Treatment of Mitochondrial Dysfunction Impact Autism Spectrum Disorder (ASD)?

Acronym

MitoASD

Official Title

Does Clinical Treatment of Mitochondrial Dysfunction Impact Autism Spectrum Disorder (ASD)?

Study Type

Interventional

2. Study Status

Record Verification Date

April 2017

Overall Recruitment Status

Unknown status

Study Start Date

March 2016 (undefined)

Primary Completion Date

June 2017 (Anticipated)

Study Completion Date

June 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Drexel University

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

In this study, 50 children between 3 and 12 years old with formally diagnosed autistic spectrum disorders (ASD) and also having significant mitochondrial dysfunction will be treated for a 3 month period with the Mitochondrial Cocktail, a combination of specific nutritional supplements and metabolite intermediates (including anti-oxidants) and bio-energy substrates. A series of neurological and psychological evaluations will be conducted by trained evaluators/clinicians to evaluate both the severity and the clinical presentation of the ASD/mitochondrial dysfunction with each subject at baseline prior to treatment, after the 3 month treatment and again at 6 months, after another 3 month non-treatment period. In addition, laboratory investigations will be conducted at the same time-points to assess the mitochondrial dysfunction and cellular biomarkers thought to be associated with autistic and mitochondrial disorders. These investigations will include the analysis of samples of blood and cheek/buccal swabs collected from each child to assess select biochemical markers of ASD. The Mitochondrial Cocktail treatment will be administered at home once a day continuously for a total of 3 months. All the children in the study will be treated with the same Mitochondrial Cocktail (an open label study).

Detailed Description

In this study, 50 children between 3 and 12 years old with formally diagnosed autistic spectrum disorders (ASD) and also having significant mitochondrial dysfunction will be treated for a 3 month period with the Mitochondrial Cocktail, a combination of specific nutritional supplements and metabolite intermediates (including anti-oxidants) and bio-energy substrates. The Mitochondrial Cocktail is presently widely used as the standard of care for clinically treating mitochondrial dysfunction. The precise content of the Mitochondrial Cocktail will be: ubiquinol (liquid form, 150 mg/kg subject weight/day carnitine, 50 mg/kg subject weight/day alpha-lipoic acid, 100 mg/ day. A series of neurological and psychological evaluations will be conducted by trained evaluators/clinicians to evaluate both the severity and the clinical presentation of the ASD/mitochondrial dysfunction with each subject at baseline prior to treatment, after the 3 month treatment and again at 6 months, after another 3 month non-treatment period. In addition, laboratory investigations will be conducted at the same time-points to assess the mitochondrial dysfunction and cellular biomarkers thought to be associated with autistic and mitochondrial disorders. These investigations will include the analysis of samples of blood and cheek/buccal swabs collected from each child to assess select biochemical markers of ASD. The Mitochondrial Cocktail treatment will be administered at home preferably in the morning once a day continuously for a total of 3 months. All the children in the study will be treated with the same Mitochondrial Cocktail (an open label study). . Safety will be also evaluated based on the occurrence of adverse events either reported spontaneously by the subject and/or caregiver or observed by the investigator(s).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Autism Spectrum Disorders, Mitochondrial Diseases

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Mitochondrial Cocktail

Arm Type

Experimental

Arm Description

The precise content of the Mitochondrial Cocktail will be: ubiquinol (liquid form, 150 mg/kg subject weight/day carnitine, 50 mg/kg subject weight/day alpha-lipoic acid, 100 mg/ day

Intervention Type

Drug

Intervention Name(s)

Mitochondrial Cocktail

Other Intervention Name(s)

Ubiqinol, Levocarnitine, Alpha Lipoic Acid

Primary Outcome Measure Information:

Title

Change in features of Autistic behavior phenotype assessed using the Social Responsiveness Scale (SRS)

Time Frame

Baseline (0), 3 and 6 months

Title

Change in Executive Function assessed using the Behavior Rating Inventory of Executive Function (BRIEF)

Time Frame

Baseline (0), 3 and 6 months

Secondary Outcome Measure Information:

Title

Changes in mitochondrial enzyme specific activities biochemically evaluated using buccal swab analysis

Time Frame

Baseline (0), 3 and 6 months

Title

Change in buccal oxidative stress markers and mitochondrial DNA (mtDNA) damage

Description

In buccal extracts, aconitase activity levels and mtDNA levels and integrity will be quantitatively evaluated at 0,3 and 6 months.

Time Frame

Baseline (0), 3 and 6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

3 Years

Maximum Age & Unit of Time

12 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subject/legal representative is considered reliable and capable of adhering to the protocol (e.g., able to understand and complete diaries), visit schedule, and medication intake according to the judgment of the investigator. . Subject has a formal diagnosis of autistic spectrum disorders (ASD). the ASD diagnosis will satisfy the DSM- V criteria for ASD, and will be broad-spectrum including both severe and milder cases. All subjects will have either suspected mitochondrial dysfunction as assessed by clinical evaluation, mitochondrial dysfunction as defined by the presence of significant abnormalities in their buccal mitochondrial respiratory complex activities (i.e., with either respiratory complex I or complex IV deficiencies) or have significantly aberrant specific activity ratios. Subjects with significant deficiencies in either muscle or skin fibroblast respiratory activities will also be included in those cases if buccal mitochondrial respiratory enzyme activity testing has not been performed. Exclusion Criteria: Subject has any medical or psychiatric condition that, in the opinion of the investigator, could jeopardize or would compromise the subject's ability to participate in this study. Subject has a medical condition that could be expected in the opinion of the investigator to interfere with drug absorption, distribution, metabolism, or excretion. Subject is on a ketogenic or other specialized diet. If the subject was on a specialized diet in the past, they must be off the diet for ≥2 months prior to the Baseline Period. Subject has an acute or sub-acutely progressive central nervous system disease. Subject has major brain deformation or severe cognitive dysfunction. Subjects with epilepsy needing to take anti-seizure medications will be excluded.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Agustin Legido, MD, PhD

Phone

215-427-5452

agustin.legido@drexelmed.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Michael J Goldenthal, PhD

Phone

215-427-6786

michael.goldenthal@drexelmed.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael J Goldenthal, PhD

Organizational Affiliation

Drexel University College of Medicine

Official's Role

Study Director

Facility Information:

Facility Name

St. Christopher's Hospital for Children

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19134

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Michael J Goldenthal, PhD

Phone

215-427-6786

michael.goldenthal@drexelmed.edu

12. IPD Sharing Statement

Learn more about this trial

Does Clinical Treatment of Mitochondrial Dysfunction Impact Autism Spectrum Disorder (ASD)?

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