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Effect of Weight Loss on Cholesterol Metabolism in Hereditary Hypercholesterolemias and Overweight or Obesity.

Primary Purpose

Familial Hypercholesterolemias, Weight Loss, Familial Combined Hypercholesterolemia

Status
Completed
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Weight loss and dietary intervention
Sponsored by
Instituto Aragones de Ciencias de la Salud
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Familial Hypercholesterolemias focused on measuring Familial Hypercholesterolemia, Familial Combined Hypercholesterolemia, Weight loss; Lipids; Phytosterols, Obesity, Overweight., Lipids

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age ≥18 years.
  • Diagnosis of Familial Combined Hyperlipidemia* and Familial Hypercholesterolemia**.
  • Body mass index > 25 kg/m2.
  • Steady weight (±3 kg in the last 3 months).
  • Absence of lipid lowering drugs including sterols supplements in the previous 5 weeks.

    • Familial Combined Hyperlipidemia diagnosis was based on the presence of primary combined hyperlipidaemia in untreated patients whose serum cholesterol and triglyceride concentrations were above the sex- and age-specific 90th percentiles for the Spanish population, serum total apolipoprotein B concentration ≥ 120 mg/dL and there was at least one first-degree relative with hyperlipidemia (total cholesterol and/or triglycerides >90th percentile) (Gómez-Gerique JA et al; 1999).

      • Familial Hypercholesterolemia was diagnosed in subjects with off-treatment LDL cholesterol concentrations above the age- and sex-specific 95th percentile of a Spanish reference population, triglyceride below 200 mg/dL and familial vertical transmission with at least one first-degree relative with LDL cholesterol above age- and sex-specific 95th percentiles (Gómez-Gerique JA et al; 1999).

Exclusion Criteria:

  • Alcohol consumption >30 gr/day.
  • Uncontrolled type-2 diabetes (HbA1c >8%).
  • Any other disease that could interfere with the ability to comply with the study protocol were excluded
  • Personal history of cardiovascular disease, very high risk as defined by the presence of ≥ 2 major risk factors, or total cholesterol ≥ 350 mg/dL since lipid-lowering drug were considered highly recommended.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Weight loss and dietary intervention

    Arm Description

    The weight loss intervention had a total duration of 6 months. Each participant's caloric prescription represented a deficit of 600 kcal per day as calculated from the person's resting energy expenditure and activity level using the Harris-Benedict equation. In general, prescribed energy intake was between 1200 kcal and 1600 kcal/day. Dietary composition consisted on 50-55% of carbohydrates, 15-20% of protein and 30% of fat and included a wide variety of foods typical of a Mediterranean diet. Patients were also provided with recipes and shopping counselling to improve intervention compliance and to achieve the weight loss goal. Individual consultations with a nutritionist were performed twice a month to motivate the weight loss and reinforce the intervention.

    Outcomes

    Primary Outcome Measures

    Change in lipids and non-cholesterol sterols concentration
    Main outcome it the variation of: Lipids: Total cholesterol, LDL cholesterol, HDL cholesterol, tryglicerides and apolipoprotein B. Non-cholesterol sterols: Phytosterols (campesterol, stigmasterol and sitosterols) and cholestanol (which are stated as subrogate markers of intestinal cholesterol absorption) and desmosterol, lathosterol and lanosterol (cholesterol synthesis markers).

    Secondary Outcome Measures

    Full Information

    First Posted
    November 21, 2013
    Last Updated
    November 25, 2013
    Sponsor
    Instituto Aragones de Ciencias de la Salud
    Collaborators
    Hospital Clinic of Barcelona, Instituto de Salud Carlos III
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01995149
    Brief Title
    Effect of Weight Loss on Cholesterol Metabolism in Hereditary Hypercholesterolemias and Overweight or Obesity.
    Official Title
    Effect of Weight Loss on Lipids Concentration and Cholesterol Metabolism in Overweight and Obese Subjects With Primary Hypercholesterolemia.
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    November 2013
    Overall Recruitment Status
    Completed
    Study Start Date
    June 2010 (undefined)
    Primary Completion Date
    September 2012 (Actual)
    Study Completion Date
    undefined (undefined)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Instituto Aragones de Ciencias de la Salud
    Collaborators
    Hospital Clinic of Barcelona, Instituto de Salud Carlos III

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    Background: Lipid lowering response to weight loss in subjects with genetic hyperlipidemias and overweight or obesity and its effect on cholesterol metabolism has not been studied. Objective: To explore the effects of weight loss on lipid values and cholesterol metabolism, by measuring circulating non-cholesterol sterols, in overweight or obese subjects with genetic hypercholesterolemias. Design: The investigators conducted a 6-months weight loss intervention in subjects with the diagnosis of familial hypercholesterolemia (FH) or familial combined hyperlipidemia (FCHL), body mass index >25 kg/m2, steady weight (±3 kg in the last 3 months) and absence of lipid lowering drugs in the previous 5 weeks. They were advised to follow a hypocaloric diet with a deficit of 600 kcal (30% fat, 15% protein, and 55% carbohydrates) per day as calculated from the person's resting energy expenditure and activity level. Anthropometric data, biochemical analysis including lipids, apolipoproteins and non-cholesterol sterols were evaluated at baseline, 3 months and 6 months.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Familial Hypercholesterolemias, Weight Loss, Familial Combined Hypercholesterolemia, Obesity
    Keywords
    Familial Hypercholesterolemia, Familial Combined Hypercholesterolemia, Weight loss; Lipids; Phytosterols, Obesity, Overweight., Lipids

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    78 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Weight loss and dietary intervention
    Arm Type
    Experimental
    Arm Description
    The weight loss intervention had a total duration of 6 months. Each participant's caloric prescription represented a deficit of 600 kcal per day as calculated from the person's resting energy expenditure and activity level using the Harris-Benedict equation. In general, prescribed energy intake was between 1200 kcal and 1600 kcal/day. Dietary composition consisted on 50-55% of carbohydrates, 15-20% of protein and 30% of fat and included a wide variety of foods typical of a Mediterranean diet. Patients were also provided with recipes and shopping counselling to improve intervention compliance and to achieve the weight loss goal. Individual consultations with a nutritionist were performed twice a month to motivate the weight loss and reinforce the intervention.
    Intervention Type
    Behavioral
    Intervention Name(s)
    Weight loss and dietary intervention
    Intervention Description
    The weight loss intervention had a total duration of 6 months. Each participant's caloric prescription represented a deficit of 600 kcal per day as calculated from the person's resting energy expenditure and activity level using the Harris-Benedict equation. In general, prescribed energy intake was between 1200 kcal and 1600 kcal/day. Dietary composition consisted on 50-55% of carbohydrates, 15-20% of protein and 30% of fat and included a wide variety of foods typical of a Mediterranean diet. Patients were also provided with recipes and shopping counselling to improve intervention compliance and to achieve the weight loss goal. Individual consultations with a nutritionist were performed twice a month to motivate the weight loss and reinforce the intervention.
    Primary Outcome Measure Information:
    Title
    Change in lipids and non-cholesterol sterols concentration
    Description
    Main outcome it the variation of: Lipids: Total cholesterol, LDL cholesterol, HDL cholesterol, tryglicerides and apolipoprotein B. Non-cholesterol sterols: Phytosterols (campesterol, stigmasterol and sitosterols) and cholestanol (which are stated as subrogate markers of intestinal cholesterol absorption) and desmosterol, lathosterol and lanosterol (cholesterol synthesis markers).
    Time Frame
    After 6 months of intervention

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Age ≥18 years. Diagnosis of Familial Combined Hyperlipidemia* and Familial Hypercholesterolemia**. Body mass index > 25 kg/m2. Steady weight (±3 kg in the last 3 months). Absence of lipid lowering drugs including sterols supplements in the previous 5 weeks. Familial Combined Hyperlipidemia diagnosis was based on the presence of primary combined hyperlipidaemia in untreated patients whose serum cholesterol and triglyceride concentrations were above the sex- and age-specific 90th percentiles for the Spanish population, serum total apolipoprotein B concentration ≥ 120 mg/dL and there was at least one first-degree relative with hyperlipidemia (total cholesterol and/or triglycerides >90th percentile) (Gómez-Gerique JA et al; 1999). Familial Hypercholesterolemia was diagnosed in subjects with off-treatment LDL cholesterol concentrations above the age- and sex-specific 95th percentile of a Spanish reference population, triglyceride below 200 mg/dL and familial vertical transmission with at least one first-degree relative with LDL cholesterol above age- and sex-specific 95th percentiles (Gómez-Gerique JA et al; 1999). Exclusion Criteria: Alcohol consumption >30 gr/day. Uncontrolled type-2 diabetes (HbA1c >8%). Any other disease that could interfere with the ability to comply with the study protocol were excluded Personal history of cardiovascular disease, very high risk as defined by the presence of ≥ 2 major risk factors, or total cholesterol ≥ 350 mg/dL since lipid-lowering drug were considered highly recommended.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Fernando Civeira, MD, PhD
    Organizational Affiliation
    Unidad de Lípidos/Laboratorio de Investigación Molecular; Hospital Universitario Miguel Servet; Instituto Aragonés de Ciencias de la Salud
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    24899155
    Citation
    Mateo-Gallego R, Perez-Calahorra S, Cofan M, Baila-Rueda L, Cenarro A, Ros E, Puzo J, Civeira F. Serum lipid responses to weight loss differ between overweight adults with familial hypercholesterolemia and those with familial combined hyperlipidemia. J Nutr. 2014 Aug;144(8):1219-26. doi: 10.3945/jn.114.191775. Epub 2014 Jun 4.
    Results Reference
    derived

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    Effect of Weight Loss on Cholesterol Metabolism in Hereditary Hypercholesterolemias and Overweight or Obesity.

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