Dietary Cholesterol and Defects in Cholesterol Synthesis in Mevalonate Kinase Deficiency - Full Text View

Sponsor:	Oregon Health and Science University
Information provided by:	Oregon Health and Science University
ClinicalTrials.gov Identifier:	NCT00260299

Purpose

Participants wanted for study of mevalonate kinase deficiency (MKD), mevalonic aciduria, or hyperimmunoglobulinemia with periodic fever syndrome (HIDS).

Patients with MKD (mevalonic aciduria or hyperimmunoglobulinemia with periodic fever syndrome (HIDS)) may be eligible for a research study conducted at Oregon Health & Science University (OHSU) in Portland, Oregon USA. The purpose of the study is to find out more about how these diseases affect body chemistry and health. The researchers also want to find out how cholesterol in the diet affect blood cholesterol and how the body handles cholesterol. This is a short-term and long-term dietary study. The long-term goal of this research is to see if controlling dietary cholesterol can decrease any of the symptoms of the diseases.

The study could involve up to 12 one-week admissions to OHSU over the course of 5 years.

Condition
Mevalonic Aciduria Mevalonate Kinase Deficiency Immune System Diseases Periodic Fever Syndromes, Hereditary Lipid Metabolism, Inborn Errors

Study Type:	Observational
Study Design:	Case-Only, Prospective
Official Title:	Dietary Cholesterol and Defects in Cholesterol Synthesis in Mevalonate Kinase Deficiency

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia beta-ketothiolase deficiency Chanarin-Dorfman syndrome cholesteryl ester storage disease familial Mediterranean fever Farber lipogranulomatosis primary carnitine deficiency succinic semialdehyde dehydrogenase deficiency

MedlinePlus related topics: Cholesterol Diets Fever

Drug Information available for: Cholest-5-en-3-ol (3beta)-

U.S. FDA Resources

Further study details as provided by Oregon Health and Science University:

Primary Outcome Measures:

Cholesterol absorption %of cholesterol intake [ Time Frame: Dec 2011 ] [ Designated as safety issue: No ]
Sterol and bile acid synthesis, mg/kg/d [ Time Frame: Dec 2011 ] [ Designated as safety issue: No ]
Mevalonate mevalonate shunt products; mg/kg/d in urine and mg/g creatinine [ Time Frame: Dec 2011 ] [ Designated as safety issue: No ]
Isoprenoids: dolichol and Coenzyme; Q mg/g Creatinine [ Time Frame: Dec 2011 ] [ Designated as safety issue: No ]
Fatty acids mg% in plasma [ Time Frame: Dec 2011 ] [ Designated as safety issue: No ]
Leukotrienes LTB4 nmol/mol creatinine [ Time Frame: Dec 2011 ] [ Designated as safety issue: No ]
Plasma cholesterol, cholestanol, desmosterol, lathosterol and sitosterol mg/dL [ Time Frame: Dec 2011 ] [ Designated as safety issue: No ]
Plasma 24-S OH-chol ng/mg cholesterol [ Time Frame: Dec 2011 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Studies of body composition/metabolism/growth (BWT, HT, head circumference) [ Time Frame: Dec 2011 ] [ Designated as safety issue: No ]
Development using several standard instruments e.g. Vineland Adaptive Behavior Scales, and Child Behavior Checklist [ Time Frame: Dec 2011 ] [ Designated as safety issue: No ]
Behavior using several standard assessments e.g. Nisonger Child Behavior Rating Form [ Time Frame: Dec 2011 ] [ Designated as safety issue: No ]
Feeding using a newly created instrument to measure feeding based on standard aspects of the neurodevelopment feeding evaluation [ Time Frame: Dec 2011 ] [ Designated as safety issue: No ]
Hearing and vision will be carried out longitudinally to document the phenotype and determine if dietary intervention is helpful [ Time Frame: Dec 2011 ] [ Designated as safety issue: No ]
Brain MRI/MRS [ Time Frame: Dec 2011 ] [ Designated as safety issue: No ]
Electroretinogram [ Time Frame: Dec 2011 ] [ Designated as safety issue: No ]
Therapeutic biomarkers for MKD: cell surface markers on T-cells, soluble markers of oxidative stress and inflammation [ Time Frame: Dec 2011 ] [ Designated as safety issue: No ]

Estimated Enrollment:	15
Study Start Date:	February 2005
Estimated Study Completion Date:	December 2011

Detailed Description:

Participants are admitted to the clinical research center for up to a week per visit. Additional visits at least yearly encouraged. During the week we measure such things as cholesterol absorption, sterol and bile acid synthesis, mevalonate and mevalonate shunt products, isoprenoids, fatty acids, leukotrienes, plasma cholesterol and other sterol levels. Also, the effects of altering dietary cholesterol on plasma 24-S OH-cholesterol, a measure of brain cholesterol turnover, will be evaluated. Studies of body composition/ metabolism/ growth, development, behavior, sleep, feeding, hearing and vision will be carried out to document the phenotype and determine if dietary intervention may be helpful.

The objective of the study is to characterize the metabolic and phenotypic consequences of MKD and study the effects of altering dietary cholesterol in MKD. We hypothesize that some of the phenotypic effects of MKD are due to altered cholesterol metabolism, but that the phenotype is predominantly due to derangements in isoprenoid metabolism.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

children or adults with mevalonic kinase deficiency/mevalonic aciduria/HIDS

Criteria

Inclusion Criteria:

Must have documented mevalonate kinase deficiency, mevalonic aciduria, or HIDS
Must be willing to participate in most research procedures

Exclusion Criteria:

Unable or unwilling to participate in most research procedures

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00260299

Contacts

Contact: Karen Smith, FNPC,MNS	503-494-7944	griersmi@ohsu.edu
Contact: Robert D Steiner, MD	503-494-2783	steinerr@ohsu.edu

Locations

United States, Oregon
Oregon Health & Science University	Recruiting
Portland, Oregon, United States, 97239
Contact: Karen Smith, FNPC,MSN 503-494-7944 griersmi@ohsu.edu
Contact: Sylvia Hathaway 503-494-2783 hathawas@ohsu.edu
Principal Investigator: Robert D Steiner, MD

Sponsors and Collaborators

Oregon Health and Science University

Investigators

Principal Investigator:

Robert D Steiner, MD

Oregon Health and Science University

More Information

No publications provided

Responsible Party:	Oregon Health & Science University ( Robert D. Steiner, MD )
Study ID Numbers:	MKD dietary study
Study First Received:	November 30, 2005
Last Updated:	October 15, 2009
ClinicalTrials.gov Identifier:	NCT00260299 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Oregon Health and Science University:

cholesterol defects
Mevalonic Aciduria
Mevalonate Kinase Deficiency
HIDS
Hyperimmunoglobulinemia with periodic fever syndrome
MKD
Lipid Metabolism, Inborn Errors

Periodic Fever Syndromes, hereditary
mevalonic acid
mevalonate kinase
cholesterol, dietary
Hyper IgD
Multiple malformations
Fever

Additional relevant MeSH terms:

Lipid Metabolism, Inborn Errors
Immunoproliferative Disorders
Autoimmune Diseases
Metabolic Diseases
Disease
Immune System Diseases
Mevalonate Kinase Deficiency
Hematologic Diseases
Blood Protein Disorders
Nervous System Diseases
Central Nervous System Diseases

Hypergammaglobulinemia
Brain Diseases
Metabolism, Inborn Errors
Pathologic Processes
Genetic Diseases, Inborn
Peroxisomal Disorders
Syndrome
Brain Diseases, Metabolic, Inborn
Familial Mediterranean Fever
Brain Diseases, Metabolic
Lipid Metabolism Disorders

ClinicalTrials.gov processed this record on November 20, 2009