Metabolic Consequences of CPT-1 Deficiency

February 24, 2010 updated by: Oregon Health and Science University

Metabolic Consequences of CPT1A Deficiency in Alaska Native Children

The purpose of this study is to learn more about how long children with CPT-1 deficiency can wait between meals without developing low blood sugar or symptoms of low blood sugar. The other purpose is to learn more about how much fat is stored in the liver of a child with CPT-1 deficiency.

Study Overview

Status

Completed

Conditions

Carnitine Palmitoyl Transferase Type 1A (CPT1A) Deficiency

Intervention / Treatment

Other: Medically supervised fasting

Detailed Description

With the advent of enhanced screening (via tandem mass spectroscopy, MS/MS), the Northwest Regional Newborn Screening Program (NWRNSP) has identified a high incidence of carnitine palmitoyl transferase type 1A (CPT1A) deficiency in Alaska Native infants. Since October of 2003 approximately 80 Alaska Native infants have been identified with this condition; previously only 30 published cases were known worldwide. All of the infants are homozygous for a c.1436C-T sequence variant in the CPT1A gene, which results in the substitution of a leucine for proline at amino acid position 479 (P479L), and an approximately 80% reduction of CPT1A activity (non-classic CPT1A deficiency) (7). The clinical implications of this very restricted level of enzyme activity are not known. However, patients with more severe reductions of CPT1A activity (as the result of other mutations) are known to be at high risk for hypoketotic hypoglycemia, liver dysfunction, and sudden unexplained death (1). Hepatomegaly with micro- and macro-vesicular steatosis is also common (16). Currently the treatment of Alaska Native infants and children with CPT1A deficiency is based on data from patients with more severe forms of CPT1A deficiency and other fatty acid oxidation (FAO) disorders. Our ultimate goal is to establish evidence-based guidelines for treatment of the form of CPT1A deficiency prevalent in the Alaska Native population. This pilot study addresses two specific questions and will provide the first glimpse of the physiologic effects of homozygosity for the c.1436C-T sequence variant in the CPT1A gene. These data will aid in the development of strategies for clinical management that can be evaluated in future prospective studies, and provide preliminary data required for applications for NIH funding for more in-depth characterization of the clinical consequences of this condition.

Study Type

Interventional

Enrollment (Anticipated)

Phase

Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- Oregon
  - Portland, Oregon, United States, 97239
    - Oregon Health & Science University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

8 months to 1 year (Child)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

Inclusion Criteria:

CPT-1 deficiency
homozygous for the c.1436C-T sequence variant
greater than 6 kg
otherwise healthy
siblings must be free of CPT-1 deficiency but heterozygous for c.1436C-T sequence variant and otherwise healthy

Exclusion Criteria:

liver dysfunction
diabetes
renal disease
metal plate in body

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Allocation: Non-Randomized
Interventional Model: Single Group Assignment
Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To compare body composition, liver and muscle lipid content, and liver function of Alaska Native children with CPT1A deficiency, with similar measures in their unaffected siblings. Time Frame: February 2009	February 2009

Secondary Outcome Measures

Outcome Measure	Time Frame
To characterize the metabolic response of Alaska Native children with CPT1A deficiency to fasting, Time Frame: February 2009	February 2009

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Oregon Health and Science University

Collaborators

Alaska Department of Health and Social Services

Investigators

Principal Investigator: Melanie B. Gillingham, PhD, Oregon Health and Science University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Gillingham MB, Hirschfeld M, Lowe S, Matern D, Shoemaker J, Lambert WE, Koeller DM. Impaired fasting tolerance among Alaska native children with a common carnitine palmitoyltransferase 1A sequence variant. Mol Genet Metab. 2011 Nov;104(3):261-4. doi: 10.1016/j.ymgme.2011.06.017. Epub 2011 Jun 28.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2007

Primary Completion (Actual)

November 1, 2008

Study Completion (Actual)

February 1, 2009

Study Registration Dates

First Submitted

April 3, 2008

First Submitted That Met QC Criteria