Gene Analysis and Treatment Optimization in Chinese Homozygous Familial Hypercholesterolemia

• Sponsor: Central South University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01878604
• Collaborator: (none)
• Enrollment: 5
• Location: 1
• Duration (Months): 159
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Identify new or novel genes which may impact on cholesterol level, and establish the relationship between those gene mutations with atherosclerosis, as well as responses to lipid-lowering drugs.

Condition or Disease	Intervention/Treatment	Phase
Homozygous Familial Hypercholesterolemia	Genetic: Gene analysis; Other: Historical data of lipid-lowering drug administration; Other: Historical data of plasma lipids, xanthoma changes

Detailed Description

To better understand the genetics basis for LDL-C elevation and develop an optimized lipid-lowering strategy, we propose to do the following studies:

1. To establish a China HoFH registry, and collect DNA and blood samples from all available family members of each proband (pedigrees);

2. To detect gene mutations known to cause FH and identify family suitable for future whole genome sequencing aimed to identify novel genes controlling cholesterol levels.

3.To establish the relationship between types of gene mutations and lipid and atherosclerosis profile, as well as responses to lipid-lowering agents.

Study Design

• Study Type: Observational
• Actual Enrollment: 5 participants
• Observational Model: Case-Only
• Time Perspective: Retrospective
• Official Title: The Study of Gene Analysis and Treatment Optimization in Chinese Homozygous Familial Hypercholesterolemia
• Study Start Date: Oct 1, 2001
• Actual Primary Completion Date: Oct 1, 2014
• Actual Study Completion Date: Jan 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Homozygous Familial Hypercholesterolemia Gene Analysis for Homozygous Familial Hypercholesterolemia cases	Genetic: Gene analysis; Gene analysis; Other: Historical data of lipid-lowering drug administration; Collecting historical data of lipid-lowering drug administration; Other: Historical data of plasma lipids, xanthoma changes; Collecting historical data of plasma lipids and xanthoma changes

Outcome Measures

Primary Outcome Measures

1. Number of LDLR Gene Mutations [1 year]

   Number of gene mutations based on the sequencing results in terms of some known genes and suspected novel genes. c.796 G>C and c.1048 C>T in the LDLR gene c.1448 G>A and c.1720C>A in the LDLR gene c.2030 G >A and c.1257 C>A in the LDLR gene homozygous mutation c.605 T>C in the LDLR gene

Secondary Outcome Measures

1. LDL-C Reduction Percentage [pre-treatment and 6-13 years post treatment]

   plasma LDL-C reduction percentage with lipid-lowering drugs from pre-treatment to the last time follow-up time point plasma LDL-C reduction percentage calculation: "plasma LDL-C at pre-treatment time point" minus "plasma LDL-C at the last time follow-up time point", and then compared with "plasma LDL-C at pre-treatment time point", namely "plasma LDL-C reduction percentage".

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

Patients of any age and sex who meet clinical or genetic criteria for hoFH as follows:

• Cutaneous xanthomata before the age of ten years

• LDLC > 13 mmol/L before treatment or > 7.76 mmol/L despite treatment

• Phenotypic features in keeping with HeFH in both parents

Exclusion criteria:

Inability of patient, or, if less than 18, a parent, to sign informed consent.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cardiology department of 2nd Xiangya Hospital	Changsha	Hunan	China	410011

Sponsors and Collaborators

• Central South University

Investigators

• Principal Investigator: Shuiping Zhao, Doctor, Central South University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Shuiping Zhao, Chief of Cardiology Department, 2nd Xiangya Hospital, Central South University
• ClinicalTrials.gov Identifier: NCT01878604
• Other Study ID Numbers: MISP50469
• First Posted: Jun 17, 2013
• Last Update Posted: Feb 20, 2017
• Last Verified: Feb 1, 2017

• Additional relevant MeSH terms: Hyperlipoproteinemia Type II; Hypercholesterolemia; Hypolipidemic Agents

Study Results

Participant Flow

Arm/Group Title	Homozygous Familial Hypercholesterolemia
Arm/Group Description	Gene Analysis for Homozygous Familial Hypercholesterolemia cases Gene analysis: Gene analysis
Period Title: Overall Study
STARTED	5
COMPLETED	5
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Patients of HoFH
Arm/Group Description	patients of Homozygous Familial Hypercholesterolemia
Overall Participants	5
Age (year) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [year]	5 (1)
Sex: Female, Male (Count of Participants)
Female	2 40%
Male	3 60%
plasma LDL cholesterol concentration (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	17.55 (2.34)

Outcome Measures

1. Primary Outcome

Title	Number of LDLR Gene Mutations
Description	Number of gene mutations based on the sequencing results in terms of some known genes and suspected novel genes. c.796 G>C and c.1048 C>T in the LDLR gene c.1448 G>A and c.1720C>A in the LDLR gene c.2030 G >A and c.1257 C>A in the LDLR gene homozygous mutation c.605 T>C in the LDLR gene
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HoFH Patients
Arm/Group Description	HoFH patients
Measure Participants	5
Number [gene mutations]	7

2. Secondary Outcome

Title	LDL-C Reduction Percentage
Description	plasma LDL-C reduction percentage with lipid-lowering drugs from pre-treatment to the last time follow-up time point plasma LDL-C reduction percentage calculation: "plasma LDL-C at pre-treatment time point" minus "plasma LDL-C at the last time follow-up time point", and then compared with "plasma LDL-C at pre-treatment time point", namely "plasma LDL-C reduction percentage".
Time Frame	pre-treatment and 6-13 years post treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HoFH Patients
Arm/Group Description	patients of Homozygous Familial Hypercholesterolemia that meet the Inclusion criteria: Cutaneous xanthomata before the age of ten years LDLC > 13 mmol/L before treatment or > 7.76 mmol/L despite treatment Phenotypic features in keeping with HeFH in both parents
Measure Participants	5
Mean (Standard Error) [percentage of plasma LDL-C reduction]	48.16 (8.5981)

Adverse Events

Adverse Event Reporting Description	Only serious adverse events were collected/assessed.
Arm/Group Title	HoFH Patients
Arm/Group Description	all HoFH patients enrolled in this study
All Cause Mortality
	HoFH Patients
	Affected / at Risk (%)	# Events
Total	0/5 (0%)
Serious Adverse Events
	HoFH Patients
	Affected / at Risk (%)	# Events
Total	0/5 (0%)
Other (Not Including Serious) Adverse Events
	HoFH Patients
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.