Vitamin Replacement in Abetalipoproteinemia

• ClinicalTrials.gov Identifier: NCT00004574
• Recruitment Status: Completed
• First Posted: December 10, 2002
• Last Update Posted: March 4, 2008
• Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by: National Institutes of Health Clinical Center (CC)

Study Description

Brief Summary:

This study will determine whether short term intravenous infusion of vitamins A and E in patients with abetalipoproteinemia can reverse disease symptoms in these patients. Abetalipoproteinemia is an inherited metabolic defect that prevents fat-soluble vitamins, such as A and E, from being absorbed from the intestines into the bloodstream and from being secreted by the liver. The deficiencies of vitamins A and E can result in severe vision impairment and a gait disorder. Treatment with megadoses of these vitamins, taken by mouth, may delay or arrest symptoms, but many continue to progress.

For this study, a single patient with moderately severe eye and neurological defects will be given essential fatty acids and fat soluble vitamins directly through a vein (intravenously) using FDA-approved replacements with a fat emulsion and multivitamins containing fat-soluble vitamins. This route of administration will bypass the digestive tract, where the absorption problem occurs. The infusions will be given twice a week for one month and then weekly for another month. Blood tests will be done weekly to measure blood lipids (fatty acids and other substances), cell counts, and vitamin levels. Eye and neurological examinations will be done once a month.

Condition or disease
Abetalipoproteinemia

Detailed Description:

Fat-soluble vitamins are normally absorbed from the diet through the gastrointestinal tract and incorporated into fat-rich particles called chylomicrons made in the intestinal wall. Chylomicrons are secreted by the intestine into the bloodstream. In a rare lipid metabolic disorder called abetalipoproteinemia, a defect in the assembly of the fat and vitamin containing particles prevents the formation of chylomicrons resulting in the malabsorption of fat and fat-soluble vitamins. A similar assembly defect of fat and fat-soluble vitamins occurs in the liver and prevents the secretion of these particles. Severe fat-soluble vitamin deficiency results even despite mega doses of oral fat-soluble vitamins. Clinically, the subjects develop neurologic and ophthalmologic symptoms similar to those in Vitamin A and E deficiency. This study is designed to determine whether short-term intravenous fat-soluble vitamins and fat emulsion can reverse the neurologic and ophthalmologic complications of fat-soluble vitamin deficiency based on noninvasive procedures routinely employed in clinical practice.

Study Design

• Study Type: Observational
• Enrollment: 1 participants
• Official Title: Vitamin Replacement in Abetalipoproteinemia
• Study Start Date: February 2000
• Study Completion Date: May 2001

Groups and Cohorts

Outcome Measures

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

None provided - protocol is intended for one patient only.

Contacts and Locations

Locations

United States, Maryland

National Heart, Lung and Blood Institute (NHLBI)

Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

More Information

Publications:

Gotto AM, Levy RI, John K, Fredrickson DS. On the protein defect in abetalipoproteinemia. N Engl J Med. 1971 Apr 15;284(15):813-8.

Ugele B, Kempen HJ, Kempen JM, Gebhardt R, Meijer P, Burger HJ, Princen HM. Heterogeneity of rat liver parenchyma in cholesterol 7 alpha-hydroxylase and bile acid synthesis. Biochem J. 1991 May 15;276 ( Pt 1):73-7.

Ikewaki K, Rader DJ, Zech LA, Brewer HB Jr. In vivo metabolism of apolipoproteins A-I and E in patients with abetalipoproteinemia: implications for the roles of apolipoproteins B and E in HDL metabolism. J Lipid Res. 1994 Oct;35(10):1809-19.

• ClinicalTrials.gov Identifier: NCT00004574
• Other Study ID Numbers: 000076; 00-H-0076
• First Posted: December 10, 2002
• Last Update Posted: March 4, 2008
• Last Verified: December 1999

Keywords provided by National Institutes of Health Clinical Center (CC):

Abetalipoproteinemia; Ataxia; Retinitis Pigmentosa; Vitamin A; Vitamin E

Additional relevant MeSH terms:

Abetalipoproteinemia; Hypobetalipoproteinemias; Hypolipoproteinemias; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases