Clinical trial NCT06178107: Efficacy of Cholesterol-lowering L. Plantarum on Cardiometabolic Health Biomarkers in Coeliac Disease Patients
Official title: UOC DI GASTROENTEROLOGIA AOU S.GIOVANNI DI DIO E RUGGI D'ARAGONA (Italy) & University of Roehampton (UK)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Celiac Disease
Keywords: PROBIOTICS, HIGH CHOLESTEROLEMIA
Lead sponsor: University of Roehampton
Sponsor class: OTHER
First posted: 2023-12-20
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a double blinded, randomised of parallel design pilot study will include 50 adults aged 18-65 with coeliac disease (CD). After an initial screening, potential subjects will be assessed for inclusion in the run-in trial.

Those subjects who meet the inclusion criteria will be then invited to the intervention study for a total duration of 9 weeks, followed by 3 weeks follow up.
Primary purpose: TREATMENT

Brief summary: Recent studies have also shown that 30% of the world's population carries the susceptibility genes for coeliac disease and that only 2-5% of these individuals are really affected, however, studies suggest the existence of other factors capable of contributing to the onset of the disease, such as intestinal dysbiosis. We have also seen how each of us has a specific microbiota, defined as an individual human enterotype, which depends on our background and can be modified by the diet. Recently, much interest has been directed to a strain of lactobacilli, called Lactobacillus plantarum (LP-LDL®) capable of reducing cholesterol and preventing the reabsorption of bile salts in the liver. The efficacy of this bacterial strain has been confirmed in 3 different human studies demonstrating the efficacy of LP-LDL® in patients with high baseline cholesterol (TC\> 6mmol / L). This is a food supplement that has been commercially available in multiple formulations in Europe for over 3 years. LP-LDP is a probiotic strain, safe to use, selected for its high bile salt hydrolase in vitro, and in vivo cholesterol reduction activity. The intake of 2 Å\~ 109 CFU encapsulated LP-LDL twice daily, significantly reduced LDL-C (13.9%), total cholesterol (TC) (37.6%), TG (53.9%), and significantly increased HDL-C (14.7%; in subjects \>60 years of age; 6-12 weeks) in normal to mildly hypercholesterolaemic subjects. In a recent double-blind placebo-controlled human study published by the Journal of Functional Foods (2022) and carried out by the University of Roehampton (UK), LPLDL showcased statistically significant reductions in multiple cardiovascular risk biomarkers, including total cholesterol, LDL cholesterol, non-HDL cholesterol and apoB. No adverse effects were noted throughout the study.

We are here proposing a pilot human intervention study to evaluate the effectiveness of the LP-LDL® probiotic in reducing cardiovascular risk factors inclusive of cholesterol in the blood in people with coeliac disease.

Detailed description: A total of 50 coeliac subjects (+/- 6 additional volunteers) will be recruited to achieve statistical significance with changes on a logarithmic scale of 1.2 for cholesterol based on other interventional studies using focused probiotics on the reduction of the lipid picture. Based on these calculations, 10 coeliac subjects are required for each study group. The Mann-Whitney U test will be used to compare variables that are not normally distributed. GraphPad Prism Version 9.0 (GraphPad Software, Inc., San Diego, CA, USA) will be used for statistical analysis. All patients with coeliac disease will be recruited at Roehampton until the set target by the Protocol (at least 25 patients will be enrolled). This is to ensure we have an acceptable number of patients that can be monitored, net of subjects lost to follow up (drop-out). A random generator (GraphPad QuickCalcs, San Diego, CA, USA) will be used in order to assign a specific number to each patient and ensure double-blind randomization of the 50 patients in two study groups. Patients will be stratified by gender and randomly assigned to one of the two treatment groups using a 2: 1 ratio due to the higher prevalence of female sex in coeliac patients.

Eligibility criteria: Inclusion criteria

* Adults aged between 18 and 65 years, with CD Diagnosis
* Fasting blood glucose level not above 5.6-6.9mmol/L
* High baseline cholesterol (TC\> 6mmol / L).
* HbA1c below 5.7%
* With cholesterol
* For intervention purposes, eligible participants are also required to have a mobile phone and be able to read and speak English.

Exclusion criteria

* People with comorbid conditions that may limit participation in the study, such as a history of an acute cardiovascular event, uncontrolled hypertension, cancer or major psychiatric or cognitive problems
* People who are already participating in a weight loss programme
* People receiving drug treatment for lipid metabolisms (e.g., statins
* People with a history of long-term use of medicines known to influence glucose metabolism (e.g., corticosteroids)
* People with elevated liver enzymes (alanine aminotransferase ≥300 IU/L, aspartate aminotransferase ≥300 IU/L)
* People who take antibiotics or bacterial agents (Probiotics) within 1 month
* Pregnant women, women ready for pregnancy, and nursing mothers

All capsules (probiotic and placebo) have the same taste and appearance and have been mixed, encapsulated and packaged to ensure product consistency throughout the study. All capsules will be distributed free of charge to participants in this study.

Primary outcomes:
measure: Change in blood cholesterol levels
timeFrame: Change from baseline to 6 and 9 weeks of the intervention
measure: Change in BMI (body mass index) Scores
timeFrame: Change from baseline to 6 and 9 weeks of the intervention
Secondary outcomes:
measure: Change in the gut microbiota diversity
timeFrame: Change from baseline to 6 and 9 weeks of the intervention
measure: Change in dietary habits
timeFrame: Change from baseline to 6 and 9 weeks of the intervention
measure: Change in VitD levels
timeFrame: Change from baseline to 6 and 9 weeks of the intervention
measure: Change in ApoB concentration
timeFrame: Change from baseline to 6 and 9 weeks of the intervention
Other outcomes:
Locations:
city: Salerno
country: Italy
facility: Uoc Di Gastroenterologia Aou S. Giovanni Di Dio E Ruggi D'Aragona
city: London
country: United Kingdom
facility: Health Sciences Research Centre, Life Sciences Department, University of Roehampton
state: UK
Study officials:
affiliation: Roehampton University
name: Adele Costabile, Prof
role: STUDY_DIRECTOR
References: