Effects of Fish Oil and Colesevelam (STAIR7007)

Study Overview
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Brief Summary
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If treatment of colesevelam, fish oil in conjunction with ezetimibe, will lead to further reduction in plasma plant sterol levels in sitosterolemia patients. We hypothesize that treatments with fish oil, colesevelam and ezetimibe will maximize decrease in plasma concentrations of sitosterol and other plant sterols in sitosterolemia patients.

Detailed Description
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Ezitimibe significantly lowers plant sterol levels in the blood of patients with sitosterolemia. However, plant sterol levels remain substantially elevated compared to those in healthy individuals. Thus, combination therapy needs to be considered. Agents that provide cardiovascular benefits such as colesevelam, a second-generation bile acid sequestrant, and fish oil are potential candidates to help further reduce sterol levels, but have yet to be evaluated in sitosterolemia patients. The purpose of this study is to dtermine the effects of colesevelam, fish oil and combination therapy (fish oil + colesevelam) on plant sterols, cholesterol and cardiovascular risk factors in sitosterolemia patients treated with ezetimibe. The results of this study will enhance knowledge on the pathogenesis of sitosterolemia and the mechanisim of actions of colesevelam and fish oil as adjunct therapies to ezitimibe in patients with the disease.

Official Title
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Effects of Fish Oil, Colesevelam and Combination Therapy on Sterol Metabolism in Sitosterolemia

Conditions
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Sitosterolemia

Intervention / Treatment
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* Drug: Colesevelam
* Dietary Supplement: Fish Oil
* Drug: Combination of fish oil and colesevelam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of homozygous sitosterolemia as established by genotyping and/or clinical parameters Receiving ezetimibe treatment Over 8 years of age (no maximum) Concomitant illnesses or conditions Exclusion Criteria: Pregnancy Intellectual disability Bowel or biliary obstruction Known hypersensitivity to colesevelam or any ingredients of colesevelam

Ages Eligible for Study
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Minimum Age: 8 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Colesevelam<br>3.75g/day for 6 weeks | Drug: Colesevelam<br>* Drug is in powder form, each packet contains 3.75g of colesevelam hydrochloride. Participant will mixed it with water and have 1 packet per day during the treatment session.<br>* Other names: Lodalis;|
| Active Comparator: Fish Oil<br>1g/day for 6 weeks | Dietary Supplement: Fish Oil<br>* In softgel form, contains 660mg EPA and 330mg DHA. Participant consume 1 softgel per day during treatment session.<br>* Other names: Omega-3;|
| Active Comparator: Combination of Fish Oil and Colesevelam<br>3.75g/day of colesevelam and 1g/day of fish oil for 6 weeks | Drug: Combination of fish oil and colesevelam<br>* combination of both colesevelam and fish oil. Participant will consume 1 packet and 1 softgel per day during treatment session.<br>* Other names: Omega-3 and Lodalis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma plant sterol level | plasma plant sterol assessment using Gas Chromatography(GC) | 32 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fatty acid | use of gas chromatography technique to measure fish oil intervention | 32 weeks | 
| endothelial functions | use of EndoPAT 2000 system to assess endothelial function | 32 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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plant sterols, cholesterol, colesevelam, phytosterolemia, fish oil