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Effect of Low-Fat Compared to Low-Carbohydrate Diet in Subjects With Multifactorial Chylomicronemia (MCMdiet)

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ClinicalTrials.gov Identifier: NCT03898609
Recruitment Status : Recruiting
First Posted : April 2, 2019
Last Update Posted : April 2, 2019
Sponsor:
Information provided by (Responsible Party):
Sophie Bernard, Institut de Recherches Cliniques de Montreal

Brief Summary:

Introduction. The multifactorial chylomicronemia ((MCM), also known as type V hyperlipoproteinaemia or mixed hyperlipidaemia) is an oligogenic or polygenic disorder that is associated with a reduction in lipoprotein lipase activity which leads to chylomicronemia. In this disease, very high concentrations of serum triglycerides (≥10 mmol/l (≥880 mg/dL)) can be observed in the fasting state due to the accumulation of both VLDL-C and chylomicron. In patients with MCM, chylomicronemia typically occur in adulthood and is exacerbated by the presence of secondary factors such as a diet rich in dietary fats and simple sugars, obesity, alcohol intake and uncontrolled diabetes. It has been estimated that chylomicronemia can be found in 1:600 adults. However, it is likely that the prevalence of MCM may increase in the future due to the increasing prevalence of obesity, metabolic syndrome and type 2 diabetes. This condition increases the risk of acute pancreatitis, which can be recurrent and potentially fatal. Indeed, the risk of acute pancreatitis is 10-20% for TG levels > 22.58 mmol/L (>2000 mg/dL). Furthermore, because MCM patients often present with other lipid disturbances as well as a worse metabolic profile, these patients are at increased risk of cardiovascular disease (CVD). Fortunately, MCM patients generally respond well to modifications in lifestyle, to treatment of secondary factors and to triglycerides lowering therapies such as fibrates. However, it is still unknown which kind of diet has the greatest effect on triglycerides level and on the metabolic profile in MCM patients.

The nutritional recommendations can be very different according to the nature of the patient's population to be treated. In order to reduce and manage triglycerides level in the general population, the American Heart Association guidelines recommend reduction of simple carbohydrates intake.

On the other hand, the nutritional intervention strategy is quite different for subjects affected by familial chylomicronemia syndrome (FCS), for which the treatment focuses on restriction of dietary fat. FCS is a very rare autosomal recessive disease that leads to a drastic reduction of chylomicrons clearance leading to chylomicronaemia. Therefore, a very strict lipid-controlled diet low in long-chain fatty acid (10-30g/day or 10%-15% of total energy intake) is required in order to lower chylomicron formation.

MCM is a complex condition in which both an increased VLDL formation by the liver and a decreased chylomicrons and VLDL clearance are present. Furthermore, triglycerides values are fluctuating from day to day but generally remain very high. Therefore, the best dietary approach for these patients remains to be elucidated.

Primary Objective. The primary objective of this study is to compare the effects of low-fat vs low-carbohydrate diets on fasting serum triglyceride concentrations.

Secondary Objectives.

  1. To compare the effects of low-fat vs low-carbohydrate diets on other fasting cardiometabolic parameters: measured LDL-C, total cholesterol, HDL-C, glucose, insulin, HOMA-IR, apoB, non-HDL-C, hs-CRP, PCSK9 and free fatty acids (FFA).
  2. To compare the effects of low-fat vs low-carbohydrate diets on SBP, DBP and waist circumference.
  3. To compare the effects of low-fat vs low-carbohydrate diets on lipoprotein subfractions (fasting).
  4. To compare the effects of low-fat vs low-carbohydrate meals on postprandial triglycerides, insulin, glucose, FFA and PCSK9 after a standardized test meal.
  5. To assess the patients' appreciation, compliance and tolerability for each experimental diet (feedback questionnaire).

Condition or disease Intervention/treatment Phase
Multifactorial Chylomicronemia (MCM) Other: Dietary intervention Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effect of Low-Fat Compared to Low-Carbohydrate Diet on Fasting Lipids and Metabolic Profile in Subjects With Multifactorial Chylomicronemia: A Randomized Crossover Study
Actual Study Start Date : January 21, 2019
Estimated Primary Completion Date : January 21, 2020
Estimated Study Completion Date : January 21, 2020

Arm Intervention/treatment
Experimental: Low-fat diet
20% fat 20% protein 60% carbohydrate
Other: Dietary intervention
3 weeks

Experimental: Low-carbohydrate diet
45% fat 20% protein 35% carbohydrate
Other: Dietary intervention
3 weeks




Primary Outcome Measures :
  1. Change of triglycerides from baseline [ Time Frame: 3 weeks ]
    Fasting serum triglyceride concentrations (mmol/L)


Secondary Outcome Measures :
  1. Change of measured LDL-C from baseline [ Time Frame: 3 weeks ]
    Fasting measured LDL-C concentrations (mmol/L)

  2. Change of total cholesterol from baseline [ Time Frame: 3 weeks ]
    Fasting total cholesterol concentrations (mmol/L)

  3. Change of HDL-C from baseline [ Time Frame: 3 weeks ]
    Fasting HDL-C concentrations (mmol/L)

  4. Change of glucose from baseline [ Time Frame: 3 weeks ]
    Fasting glucose concentrations (mmol/L)

  5. Change of insulin from baseline [ Time Frame: 3 weeks ]
    Fasting insulin concentrations (pmol/L)

  6. Change of apolipoprotein B from baseline [ Time Frame: 3 weeks ]
    Fasting apolipoprotein B concentrations (g/L)

  7. Change of hs-CRP from baseline [ Time Frame: 3 weeks ]
    Fasting hs-CRP concentrations (mg/L)

  8. Change of PCSK9 from baseline [ Time Frame: 3 weeks ]
    Fasting PCSK9 concentrations (ng/mL)

  9. Change of free fatty acids from baseline [ Time Frame: 3 weeks ]
    Fasting free fatty acids concentrations (mEq/L)

  10. Change of systolic blood pressure from baseline [ Time Frame: 3 weeks ]
    Measurement of systolic blood pressure (mmHg)

  11. Change of diastolic blood pressure from baseline [ Time Frame: 3 weeks ]
    Measurement of diastolic blood pressure (mmHg)

  12. Change of waist circumference from baseline [ Time Frame: 3 weeks ]
    Measurement of waist circumference (cm)

  13. Change in the composition of lipoprotein fractions from baseline [ Time Frame: 3 weeks ]
    Ultracentrifugation and lipoprotein electrophoresis

  14. Postprandial triglycerides [ Time Frame: One day ]
    After a standardized test meal (1h, 2h, 4h and 6h) (mmol/L)

  15. Postprandial insulin [ Time Frame: One day ]
    After a standardized test meal (1h, 2h, 4h and 6h) (pmol/L)

  16. Postprandial glucose [ Time Frame: One day ]
    After a standardized test meal (1h, 2h, 4h and 6h) (mmol/L)

  17. Postprandial free fatty acids [ Time Frame: One day ]
    After a standardized test meal (1h, 2h, 4h and 6h) (mEq/L)

  18. Postprandial PCSK9 [ Time Frame: One day ]
    After a standardized test meal (1h, 2h, 4h and 6h) (ng/mL)

  19. Questionnaire of appreciation, compliance and tolerability [ Time Frame: 3 weeks ]
    The patients' appreciation, compliance and tolerability for each experimental diet will be collected in a questionnaire



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Men or women ≥ 18 years
  2. Fasting triglycerides values ≥ 10 mmol/L (≥ 880 mg/dL) at screening.

Exclusion Criteria:

  1. A diagnosis of familial chylomicronemia syndrome, familial hypercholesterolemia or type III hyperlipidemia.
  2. An episode of accute pancreatitis in the 6 months prior the screening.
  3. The use of lipid-lowering medication in the 4 weeks prior the screening such as fibrates or statins.
  4. Recent changes (in the last 3 months) in other medication or supplement known to affect lipid or glucose metabolism such as steroid, antiretroviral therapy or oral contraceptive.
  5. Any condition known to affect lipid or glucose metabolism such as uncontrolled diabetes, nephrotic syndrome, Cushing's syndrome, hypothyroidism.
  6. Major surgery in the 3 months preceding the study.
  7. Significant weight change (±10 %) within 3 months prior to beginning the study.
  8. Inability to reduce alcohol use ( 0 - 2 units per week)
  9. The necessity or the wish to follow a specific diet.
  10. BMI ≥ 40 kg/m2.
  11. Pregnancy or the wish to become pregnant.
  12. Breastfeeding
  13. Consumption of dietary supplements such as omega-3, psyllium or phytosterols.
  14. Any serious health condition associated with a life expectancy of ≤ 1 year.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03898609


Contacts
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Contact: Manon Fantino, RD, BSc 514-987-5650 manon.fantino@ircm.qc.ca
Contact: Martine Paquette, RD, MSc 514-987-5507 martine.paquette@ircm.qc.ca

Locations
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Canada, Quebec
Institut de recherches cliniques de Montreal Recruiting
Montreal, Quebec, Canada, H2W1R7
Contact: Manon Fantino, RD, BSc    514-987-5507    manon.fantino@ircm.qc.ca   
Contact: Martine Paquette, RD, MSc    514-987-5507    martine.paquette@ircm.qc.ca   
Principal Investigator: Sophie Bernard, MD, PhD         
Sub-Investigator: Alexis Baass, MD, MSc         
Sponsors and Collaborators
Institut de Recherches Cliniques de Montreal
Investigators
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Principal Investigator: Sophie Bernard, MD, PhD Institut de Recherches Cliniques de Montreal (IRCM)

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Responsible Party: Sophie Bernard, Director of the Lipids, Nutrition and Cardiovascular Prevention Clinic of the Montreal Clinical Research Institute (IRCM), Institut de Recherches Cliniques de Montreal
ClinicalTrials.gov Identifier: NCT03898609     History of Changes
Other Study ID Numbers: 2019-957
First Posted: April 2, 2019    Key Record Dates
Last Update Posted: April 2, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No