Dietary Cholesterol and Defects in Cholesterol Synthesis in Mevalonate Kinase Deficiency

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.

Study Overview

• Status: Terminated
• Conditions: Immune System Diseases; Lipid Metabolism, Inborn Errors; Mevalonic Aciduria; Mevalonate Kinase Deficiency; Periodic Fever Syndromes, Hereditary

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.

• Study Type: Observational
• Enrollment (Actual): 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the effects of dietary cholesterol changes in MKD on cholesterol and related synthetic pathways	blood levels of cholesterol	December 2011

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Define genotype, phenotype and response to dietary cholesterol. Determine genotype-therapy correlations.	Gene Mutations - 7-dehydrocholesterol levels	December 2011

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Investigators: Principal Investigator: Robert D Steiner, MD, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start: February 1, 2005
• Primary Completion (Actual): December 31, 2014
• Study Completion (Actual): January 31, 2016

Study Registration Dates

• First Submitted: November 30, 2005
• First Submitted That Met QC Criteria: November 30, 2005
• First Posted (Estimate): December 1, 2005

Study Record Updates

• Last Update Posted (Actual): May 24, 2019
• Last Update Submitted That Met QC Criteria: May 22, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Fever; HIDS; Lipid Metabolism, Inborn Errors; cholesterol defects; Mevalonic Aciduria; Mevalonate Kinase Deficiency; Hyperimmunoglobulinemia with periodic fever syndrome; MKD; Periodic Fever Syndromes, hereditary; mevalonic acid; mevalonate kinase; cholesterol, dietary; Hyper IgD; Multiple malformations
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Immunoproliferative Disorders; Disease; Hematologic Diseases; Genetic Diseases, Inborn; Blood Protein Disorders; Hereditary Autoinflammatory Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Hypergammaglobulinemia; Peroxisomal Disorders; Syndrome; Metabolism, Inborn Errors; Immune System Diseases; Familial Mediterranean Fever; Lipid Metabolism, Inborn Errors; Mevalonate Kinase Deficiency
• Other Study ID Numbers: MKD dietary study