Clinical trial NCT05038436: Influence of Polyglucosamine L112 on Serum Surrogate Markers of Cholesterol Absorption
Official title: Influence of a Medical Device (Polyglucosamine L112) on Serum Surrogate Markers of Cholesterol Absorption: a Prospective Placebo-controlled, Randomised, Double-blind Cross-over Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cholesterol Lowering
Keywords: obesity
weight reduction
cholesterol reduction
Lead sponsor: Certmedica International GmbH
Sponsor class: INDUSTRY
Collaborators: name: University Hospital, Bonn
First posted: 2021-09-09
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: prospective, randomised, double blind, placebo controlled, 2 period crossover, monocenter
Primary purpose: BASIC_SCIENCE

Brief summary: Obesity is widespread and the number of overweight people has tripled from 1975 to 2016. According to the WHO (World Health Organisation), 1.9 billion adults worldwide are overweight, of which 650 million are obese. Thus, obesity is caused by a balance problem between the amount of food consumed and the energy used. The weighting of the diet in favour of a far too high fat intake also has a negative influence on the fat metabolism.

Obesity is associated with a number of secondary diseases, such as diabetes mellitus, increased inflammatory parameters in the blood and a higher risk of heart attack and stroke. These secondary diseases reduce the quality and duration of life of the person affected.

In animal studies, polyglucosamine was found to have a cholesterol-lowering effect. In human studies conducted over 3 and 12 months, formoline L112 was shown to lower LDL levels in the blood.

For research purposes, the present study will focus on investigating whether the intake of polyglucosamine L112 leads to a reduction in cholesterol intake from food, which should result in a reduced fat and thus calorie intake.

Detailed description: In the present study, the influence of polyglucosamine L112 on cholesterol absorption in humans is to be investigated in more detail.

For this purpose, the subjects undergo two randomised study periods in a crossover design: first, there is a 2-week run-in phase, during which baseline values are collected without influence, then the subjects undergo two identical study periods, during which the subjects randomly take either polyglucosamine L112 or placebo twice a day. The study periods are separated by a two-week washout phase. After two weeks, a final examination takes place.

Throughout the course of the study, lipids in the serum are measured regularly. In order to examine cholesterol absorption, however, it is not sufficient to determine the cholesterol levels in the blood, as reduced absorption is physiologically compensated for by increased endogenous synthesis.

In the present study, the plant sterol campesterol, which is absorbed from the intestine like cholesterol, is determined as a surrogate marker for cholesterol absorption. At the same time, a surrogate marker for endogenous cholesterol synthesis is determined with lathosterol, which behaves like the endogenously synthesised cholesterol in terms of concentration. However, campesterol must also be set in relation to cholesterol via the campesterol-cholesterol quotient, since the concentration of campesterol is also dependent on the concentration of LDL lipoproteins as transport molecules, which reacts in the same way as the cholesterol concentration. Accordingly, a lower value of the campesterol-cholesterol quotient indicates reduced cholesterol absorption.

The values corrected for total cholesterol then give an overview of the endogenous cholesterol synthesis for the cholesterol precursors, that of the plant sterols via the cholesterol resorption rate in the small intestine and that of the oxysterols via the bile acid synthesis rate.

Eligibility criteria: Inclusion Criteria:

* Subjects must be ≥ 18 years and ≤ 65 years of age at the time of the screening examination.
* Written documented informed consent and consent to participate in the study.
* Body weight must be ≥ 75 kg at the time of the screening examination.
* Balanced omnivorous diet
* Subjects who are able to follow study instructions and are likely to attend all required study visits (compliance)
* Women of childbearing age must use a reliable method of contraception during treatment
* Negative pregnancy test

Exclusion Criteria:

* BMI \< 20 and \> 30
* Subject is unable to understand the scope, significance and consequences of this clinical trial
* known hypersensitivity to crustaceans or any of the ingredients of polyglucosamine L112
* concurrent participation in another clinical trial or participation in a clinical trial involving the use of an investigational product for up to 30 days prior to participation in this trial
* known or suspected abuse of medications, drugs, or alcohol
* existing or planned pregnancy or lactation
* not using any contraceptive measure
* previous or active malignant disease
* liver or kidney dysfunction
* history of or clinical evidence of heart failure
* History of lactose intolerance
* Serum laboratory parameters:
* TSH not within normal range
* Creatinine not within normal range
* Bilirubin not within normal range
* Alkaline phosphatase not within normal range
* ALT/AST \> 1.5xULN (upper normal limit)
* LDL cholesterol \< 130 and \>180 mg/dl
* Triglycerides \> 200 mg/dl
* HbA1c \> 6.5
* Campesterol in serum \> 1 mg/dl
* Intake of food supplements (e.g. Becel Proactive)
* Contraindications for weight-reducing therapy
* Pure vegan diet
* Pure meat diet
* Diabetes mellitus type I and II
* Serious gastrointestinal diseases (ulcerative colitis, Crohn's disease, diverticulitis, short bowel syndrome, gastric ulcer, pronounced irritable bowel syndrome, reflux treated with medication, etc.) and after operations in the gastrointestinal tract (except: appendectomy)
* chronic digestive problems (constipation, constipation, etc.)
* Any other disease or medical treatment that, in the opinion of the investigator, could interfere with the assessment of safety, tolerability or efficacy.
* Current medication
* Lipid-lowering drugs such as statins, fibrates, ezitimib or PCSK9 inhibitors
* Interactions with polyglucosamine L112 are expected with the following medications: lipophilic oral medications such as cerebrally active drugs (including antiepileptics), lipophilic hormones (including the contraceptive pill), lipophilic antibiotics, digitalis, fat-soluble vitamins (A, D, E, K), (poly)unsaturated fatty acids.

Exception: Participation in the study is possible if medicinal products for which an interaction is to be expected or cannot be ruled out can be taken at least 4 hours apart from polyglucosamine L112. I.e. since the test product must be taken with the main meals, participation in the study can only take place if it is not necessary to take it with the two main meals.

* taking proton pump inhibitors
* Long-term medication that reduces bowel activity (e.g. opiates)
* Subjects who are dependent on corticosteroids and who cannot be discontinued in time 10 days before the start of the study.
* Taking vitamin K antagonists or other anticoagulants
* Not taking stable medication that can lead to weight gain (e.g. certain neuroleptics, beta-blockers, psychotropic drugs)
* Taking orlistat
* Deliberate weight reduction \>10 kg within the last 5 months
* Unintentional weight reduction within the last 5 months \> 5 kg

Primary outcomes:
measure: Influence of polyglucosamine L112 on dietary cholesterol absorption
timeFrame: 10 weeks
Secondary outcomes:
measure: Influence of polyglucosamine L112 on surrogate markers of cholesterol
timeFrame: 10 weeks
measure: Influence of polyglucosamine L112 on cholesterol synthesis
timeFrame: 10 weeks
measure: Influence of polyglucosamine L112 on bile acid synthesis
timeFrame: 10 weeks
measure: Influence of polyglucosamine L112 on neutral fecal sterols
timeFrame: 10 weeks
measure: Fecal primary and secondary bile acids
timeFrame: 10 weeks
measure: Cholesterol measurements
timeFrame: 10 weeks
measure: Change in body weight
timeFrame: 10 weeks
measure: Safety and tolerability (i.e. incidents of treatment-emergent adverse events) of polyglucosamine L112
timeFrame: 10 weeks
Other outcomes:
Locations:
city: Bonn
country: Germany
facility: Phase I-Unit, Study Center Bonn (SZB), University Hospital Bonn
state: North-Rhine Westfalia
Study officials:
affiliation: University Hospital Bonn, Germany
name: Martin Coenen, MD
role: PRINCIPAL_INVESTIGATOR
References: