Cholesterol Absorption Inhibition Study

NCT01138787 | Completed

• 1 other identifier: 09030V
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale: Consuming Plant Sterols (PS) fortified foods is widely accepted as easy to apply, life-style change to combat modestly elevated plasma cholesterol concentrations. PS are typically formulated as PS fatty acid ester (PSE) from margarines. In this study, PS will be formulated in a new innovative type spread. To confirm that the new spread results in a comparable cholesterol absorption inhibition as the reference product a dual isotope cholesterol study is planned, prior to any larger efficacy study. Primary objective: Cholesterol absorption inhibition (%) calculated from plasma concentration vs. time curves from labeled cholesterol, for the PS or PSE containing products, compared to a control product without PS or PSE. Secondary objectives: PK parameters for cholesterol as derived from the plasma concentration vs. time curves. Study design: Acute, single dose, double-blind, randomized, cross-over. Study population: 18 healthy, non-obese men (BMI 20-27 kg∙m-2, age range 20 - 65 yr) Test products: PS (2250 mg) formulated in innovatively processed spread (30 g); PSE (2250 mg PS) reference product (30 g); Control product without PS or PSE (30 g) Intervention: Three study periods during which a single dose of either Test, Reference or Control (regular light spread) spreads will be consumed together with standard breakfast. At each study period, 50 mg of D7-cholesterol is added to the meal and 30 mg of 13C-cholesterol is injected to measure cholesterol absorption. Before and four times after consumption of each spread, blood samples will be taken at 24 h intervals up to 7 days. Key parameters: Enrichments of labeled cholesterol isotopes as determined by GCMS and IRMS. Fractional absorption is determined by the ratio of the two isotopes in plasma cholesterol after 7 days.

Conditions

Cholesterol Absorption Inhibition

Outcome Measures

Primary Outcomes (1)

• cholesterol absorption calculated from plasma cholesterol enrichments vs. time curves

  5 blood samples within one week for each intervention

Secondary Outcomes (1)

• PK parameters derived from plasma curves (Cmax, Tmax, cholesterol pool, flux).

  5 blood samples within one week for each intervention

Study Arms (3)

Reference spread

ACTIVE COMPARATOR

2250 mg PS (as PSE) in spread (30 g) * 50 mg labeled D7-cholesterol, * 30 mg 3,4-13C-cholesterol, iv dosed at same time.

Dietary Supplement: Reference spread

Placebo spread

PLACEBO COMPARATOR

regular light margarine (30 g) * 50 mg labeled D7-cholesterol, * 30 mg 3,4-13C-cholesterol, iv dosed at same time.

Dietary Supplement: Placebo spread

Test spread

EXPERIMENTAL

2250 mg PS in innovatively processed spread (30 g) * 50 mg labeled D7-cholesterol, * 30 mg 3,4-13C-cholesterol, iv dosed at same time.

Dietary Supplement: Test spread

Interventions

Reference spread DIETARY_SUPPLEMENT

Single dose (30 gr) of spread, containing 2250 mg PS

Reference spread

Placebo spread DIETARY_SUPPLEMENT

Single dose (30 gr) of regular light margarine

Placebo spread

Test spread DIETARY_SUPPLEMENT

Single dose (30 gr) of innovatively processed spread containing 2250 mg PS.

Test spread

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Apparently healthy: no medical conditions which might effect study measurements (judged by study physician).
• Males aged 20 - 65
• BMI 20-27 kg∙m-2
• LDL-C levels between 3.0 - 5.0 mmol/L, triglycerides \< 3.0 mmol/L
• Not more than 10 hours per week of strenuous exercise
• Ability to give informed consent.
• Ability to follow verbal and written instructions.
• Non-smoker (tobacco, marijuana).
• The ability to attend and to commute to the performance site for each of study day visit and follow-up throughout the study period are required.
• Willing to consume a breakfast in the morning of each study day.
• Willing to consume margarine on each study occasion.
• Having a general practitioner.
• No use of medication which interferes with study measurements (as judged by the study physician).
• Agreeing to be informed about medically relevant personal test-results after the screening visit by a physician.
• Consumption =\< 21 alcoholic drinks in a typical week.

You may not qualify if:

• Unwilling to refrain from consumption of plant sterol or stanol containing products one week before and during the study..
• Plasma lipid profile which indicates deviating lipid / cholesterol homeostasis, to be judged by study physician.
• Evidence of severe cardiovascular, respiratory, urogenital, gastrointestinal/ hepatic, hemato¬logical/ immunologic, HEENT (head, ears, eyes, nose, throat), dermatological/ connective tissue, musculoskeletal, metabolic/nutritional, endocrine, neurological/ psychiatric diseases, allergy, major surgery and/or laboratory assessments which might limit participation in or completion of the study protocol.
• Gastrointestinal or hepatic disorders influencing gastrointestinal absorption or transit, including gallstones or biliary diseases.
• History of surgery related to the gastro-intestinal tract
• On a medically prescribed or weight reduction diet
• Recreational (intravenous) drug use.
• The use of psychotropic drugs, including: benzodiazepines or alcohol in excess of 21 units/ week for males
• Concomitant medication that may modulate gastro-intestinal secretions and pH (e.g. antacids, proton-pump-inhibitors, prostaglandins, anticholinergic agents, H2-receptor antagonists)
• Concomitant medication that can alter gastric emptying (e.g. metoclopramide, cisapride, domperidone and erythromycin, anticholinergics, tricyclic antidepressants, narcotic analgesics, adrenergic agents, calcium channel blockers)
• Concomitant medication that can alter intestinal transit (e.g. loperamide, chemical/ osmotic/bulk laxatives), or influence satiety/energy intake (e.g. sibutramine, gluco¬corticoids, anabolic steroids)
• Intolerance or allergy for test product.

Sponsors & Collaborators

• Unilever R&D: lead
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator

Study Sites (1)

Academisch Medisch Centrum, vasculaire geneeskunde

Amsterdam, North Holland, Netherlands

Location

Study Officials

• Maud N Vissers, Dr. Ir

  Academisch Medisch Centrum, afdeling vasculaire geneeskunde

  PRINCIPAL INVESTIGATOR

• Guus SM Duchateau, Dr

  Unilever Research & Development Vlaardingen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: June 4, 2010
• First Posted: June 7, 2010
• Study Start: June 1, 2010
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: May 4, 2017

Record last verified: 2017-05

Locations

NL (1)