Plant Sterol INtervention for Cancer Prevention (PINC)

NCT04147767 | Unknown

• 1 other identifier: RD19/123502
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Several types of human cells convert cholesterol into other molecules, including oxysterols. Oxysterols can promote breast cancer growth and help tumours to spread. Some breast cancer types recruit other cells (host cells) able to produce oxysterols within the local cancer environment. How these other cells help breast tumours metastasize or resist chemotherapy is not well understood, but epidemiological and clinical studies suggest elevated LDL-C is associated with worse survival, poorer response to therapy and an increased propensity for disease relapse in breast cancer patients. In this trial the investigators will test how an LDL-C lowering dietary intervention (using commercially available phytosterol added food products), alters the ability of non-cancer cells (adipocytes, fibroblasts and macrophages) collected from high LDL-C volunteers to change chemotherapy response and metastatic process in breast cancer cells. In this trial, volunteers with high LDL-C levels will be recruited by the University of Leeds, and divided randomly into two arms that cross over. The experimental period (yogurt drink enriched with phytosterols) and placebo period (non-enriched yogurt drink) will each last for 8 weeks, alternated with a 4 weeks of wash-out period. Samples will be collected 4 times (week-0, week-8, week-12, week-20) during the study and will include blood, white blood cells (macrophages), and fat tissue cells. Measurements will include oxysterol, LDL-C and phytosterol concentrations (volunteers' serum/plasma, media from the host cells/breast cancer experimental culture) and how the host cells alter the behaviour of cancer cells in the laboratory.

Conditions

Hypercholesterolemia; Breast Cancer; Obesity

Keywords

oxysterol; breast cancer; phytosterols; cholesterol metabolism

Outcome Measures

Primary Outcomes (1)

• To change circulating oxysterols levels after phytosterols intervention.

  The changes of oxysterols content in serum/plasma after 8 weeks of phytosterols intervention compared to placebo. After the dietary intervention, we expect to observe a change of -20% in circulating 27-hydroxycholesterol content (marker of oxysterols systemic levels). Concentration of oxysterols using LC-MS/MS measurement of plasma in 50 subjects after placebo and after intervention.

  Serum/plasma oxysterols concentrations will be measured during all the steps of the trial (baseline, 8th week, 12nd week, 20th week)

Secondary Outcomes (9)

• Change intra-cellular adipocyte and macrophages oxysterols concentrations

  Serum/plasma/medium oxysterols concentrations will be measured during all the steps of the trial (baseline, 8th week, 12nd week, 20th week)

• Study of adipocytes and macrophages interaction with breast cancer cell lines

  Protein expression will be measured during all the steps of the trial (baseline, 8th week, 12nd week, 20th week)

• Study of adipocytes and macrophages interaction with breast cancer cell lines

  Gene expression will be measured during all the steps of the trial (baseline, 8th week, 12nd week, 20th week)

• Study the effect of phytosterols on LDL-C

  Serum/plasma phytosterols and lipid concentrations will be measured during all the steps of the trial (baseline, 8th week, 12nd week, 20th week)

• Study the effect of phytosterols on HDL-C

  Serum/plasma phytosterols and lipid concentrations will be measured during all the steps of the trial (baseline, 8th week, 12nd week, 20th week)

Other Outcomes (2)

• Study RNA sequences changes in the oxysterols/LDL-C pathway and secondary breast cancer before and after phytosterols intervention .

  RNA will be studied during all the steps of the trial (baseline, 8th week, 12nd week, 20th week)

• Study changes in the interactions between proteins and DNA in the oxysterols/LDL-C pathway and secondary breast cancer before and after phytosterols intervention .

  interactions between proteins and DNA will be studied during all the steps of the trial (baseline, 8th week, 12nd week, 20th week)

Study Arms (2)

Phytosterols Arm

EXPERIMENTAL

The investigational food product "Cholesterol Reducing Strawberry Yogurt Drink (Tesco)" is a strawberry yogurt drink with added plant sterols. A 100g bottle (one serving) of cholesterol lowering strawberry yogurt drink contains 2g of free plant sterols. The magnitude of the effect given by this enriched food product, providing a daily intake of 1,5-2,4 g plant sterols/stanols, refers to the lowering/reducing blood cholesterol effects in the range "7 % to 10 %" within 2 to 3 weeks of treatment, as specified by Commission Regulation (EU) 384/2010 of 05/05/2010. The dietary intervention will consist in 8 weeks consumption of PSS enriched Yogurt Drink, which provide a daily PSS intake of 3.4g/100g bottle plant sterols ester equivalent to 2g/100g bottle of free plant sterols.

Dietary Supplement: Cholesterol Reducing Strawberry Yogurt Drink (Tesco Ltd)

Placebo Arm

PLACEBO COMPARATOR

The investigational food product "Low Fat Strawberry Yogurt Drinks (Morrisons)" is a strawberry flavoured yogurt drink with sweetener and sugar, vitamin C, B6 and D, British milk. Placebo intervention consists in 8 weeks consumption of PSS non-enriched Yogurt Drinks. The placebo intervention is needed for the study design chosen (randomized double-blind placebo-controlled cross-over clinical trial). Placebo will be used in order to determine the efficacy of PSS intervention, comparing the effects of the two compounds (PSS and placebo) in the same experimental conditions and then avoiding bias.

Dietary Supplement: Low Fat Strawberry Yogurt Drinks (Morrisons Ltd)

Interventions

Cholesterol Reducing Strawberry Yogurt Drink (Tesco Ltd) DIETARY_SUPPLEMENT

Ingredients: Skimmed Milk, Strawberry Juice from Concentrate (5%), Plant Sterols Ester (3.4%)\*\*\*, Sugar, Maize Starch, Flavourings, Colour (Anthocyanins), Starter Culture including Bifidobacterium (Milk), Thickener (Carob Gum), Sweetener (Sucralose), Milk Proteins. \*\*\* Equivalent to 2% Free Plant Sterols

Phytosterols Arm

Low Fat Strawberry Yogurt Drinks (Morrisons Ltd) DIETARY_SUPPLEMENT

Ingredients: Yogurt (Milk), Water, Sugar, Strawberry Purée (1%), Modified Maize Starch, Carrot Concentrate, Flavouring, Acidity Regulator (Citric Acid), Vitamin C, Colour (Paprika Extract), Sweetener (Sucralose), Vitamin D, Vitamin B6.

Placebo Arm

Eligibility Criteria

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

You may qualify if:

• Subjects capable of giving informed consent;
• Non-pregnant, non-nursing female;
• Age between 18-65 years old;
• LDL-C ≥130mg/dL (3.4mmol/L) or TC/HDL ratio \>4;
• BMI ≥25 (kg/m2)

You may not qualify if:

• Subjects who are under treatment with lipophilic statins;
• Subjects under any other supplementation that improve cholesterol levels (i.e. monacolin, other PSS enriched products);
• Subjects under any weight loss or lipid lowering dietary plan;
• Present or past chronic diseases: CVDs, cancer, know positive hepatitis B virus surface antigen (HBsAg), hepatitis C (HCV) antibody or HIV, cirrhosis, gastrointestinal disorders (i.e. irritable bowel syndrome, Crohn's disease, celiac disease, bowel control problems), kidney diseases, autoimmune diseases, endocrine disorders, metabolic diseases (i.e. diabetes type I and type II, familiar hypercholesterolemia), neurological diseases;
• Diagnosed eating disorders according to the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5);
• Past or planned within the trial period bariatric surgery;
• Past or planned within the trial period gastrointestinal resections;
• Corticosteroid and chronic inflammatory therapy;
• Consumption within the preceding 8 weeks of other compounds capable of influencing cholesterol metabolism (bile acid-binding resins, ezetimibe, psyllium, fish oil supplements, soya lecithin, phytoestrogens and other PSS-fortified foods);
• Females pregnant or females who are planning pregnancy;
• Females breastfeeding;
• Phytosterolemia diseases;
• Participants with allergies to any of the substances presents in the yoghurt drink chosen for the trial: citric acid, anhydrous, sodium chloride, disodium edetate dehydrate, polysorbate 80, sodium hydroxide, Hypersensitivity to E. Coli derived proteins, nuts, peanuts, egg and soy proteins. Participants with a latex allergy are also not eligible as the inner needle cover of the pre-filled syringe contains dry natural rubber (a derivative of latex);
• Participants with allergies to lidocaine;
• Participation in other dietary or clinical trials.

Sponsors & Collaborators

• University of Leeds: lead
• The Leeds Teaching Hospitals NHS Trust: collaborator
• University of Oslo: collaborator

Study Sites (1)

University of Leeds

Leeds, West Yorkshire, LS29JT, United Kingdom

RECRUITING

MeSH Terms

Conditions

Hypercholesterolemia; Breast Neoplasms; Obesity

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• James L Thorne, PhD

  University of Leeds

  PRINCIPAL INVESTIGATOR

Central Study Contacts

James L Thorne, PhD

CONTACT

+440113343 0684; J.L.Thorne@leeds.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All trial investigators will be blinded to the intervention, except for the CI. The CI will keep a record of interventions administrated. All trial participants and outcome assessors will be blinded to the intervention. Each food product has the same flavour and taste, as well as the same packaging to ensure blinding in maintained throughout study.
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Investigator

Model Details: Enrolled participants will undergo 1:1 simple randomisation by the CI, to either Experimental arm or placebo arm.. Evaluations after intervention will be made at the end of the first 8 weeks of intervention (Day 56; 8th week) and at the end of the second 8 weeks intervention (Day 140; 20th week). Since a wash out period between the two food products consumption is provided, another evaluation after wash out period (Day 84; 12th week) will be performed. The wash out period consist in a 4 weeks food products free period, where will be ask to participants to maintain their usual dietary and life style habits excluding the consumption of any yoghurt drinks.

Study Record Dates

• First Submitted: October 21, 2019
• First Posted: November 1, 2019
• Study Start: February 10, 2020
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: May 20, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)