HypercholesterolemiaPINCNCT04147767
Plant Sterol INtervention for Cancer Prevention (PINC)
A study testing Cholesterol Reducing Strawberry Yogurt Drink (Tesco Ltd) and Low Fat Strawberry Yogurt Drinks (Morrisons Ltd) in people with Hypercholesterolemia and Breast Cancer, run by University of Leeds at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Hypercholesterolemia, Breast Cancer, Obesity
- What is being tested?
- Cholesterol Reducing Strawberry Yogurt Drink (Tesco Ltd) and Low Fat Strawberry Yogurt Drinks (Morrisons Ltd)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 10 Feb 2020to 31 Dec 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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;
Show all 15Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
University of Leeds
Leeds, West Yorkshire, LS29JT
James L Thorne, PhD, +440113 343 0684, J.L.Thorne@leeds.ac.uk
Giorgia, PhD, +440113 343 7724, G.Cioccoloni@leeds.ac.uk
About this study
Official title: Randomised Control Cross-over Trial to Test How Dietary Plant Sterols Modify Tumour Promoting Capabilities of Non-tumour Host Cells in Volunteers With Elevated LDL-C
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.
Read the detailed description
Delivery of cholesterol to extra-hepatic tissues by LDL has a profound impact on different host cell types, many of which themselves have been implicated in BCa metastasis and chemoresistance.
Despite accumulating data, it is still unknown how host-cells help breast tumours metastasise or evade chemotherapy. The molecular link between cholesterol and metastasis may involve the enzymatic hydroxylation (an intermediate step in bile acid synthesis) of cholesterol. The synthesis and secretion of oxysterols into the tumour microenvironment and this is exacerbated in individuals with elevated LDL-cholesterol. This process, occurring largely in macrophages, adipocytes and fibroblasts, leads to biosynthesis and cellular export of oxysterols , which drive DNA mutations through oxidative stress, confer resistance to chemotherapy, enhance BCa growth and metastasis, and are elevated in serum of BCa patients at metastatic relapse. Our pilot data show non-cancer host-cells activate oxysterols signalling and drug resistance protein expression and confer chemotherapy resistance in adjacent cancer cells.
The investigators therefore propose to test the hypothesis that the reason epidemiological and clinical studies find elevated LDL-C and its co-morbidities associate with worse survival in BCa patients, is because the host-cells of these patients have enhanced cholesterol metabolic flux leading to increased oxysterols production and improved tolerance of chemotherapy and promotion of cancer metastatic pathways.
This trial is a multicentre cross-over double blind clinical trial in which volunteers with LDL-C ≥160mg/dL (4.1 mmol/L), recruited at the University of Leeds and/or identified through Horizon 2020 project PATHWAY-27, will be randomised into two arms of intervention, Group A (experimental arm) will be given an yoghurt drink enriched with PSS and Group B (placebo comparator) will be given yoghurt drink non-enriched with PSS. Each dietary intervention will last for 8 weeks, alternated with a 4 weeks of wash out period. This trial wants to highlight the superiority of the PSS (yoghurt drink enriched) to placebo (yoghurt drink non-enriched) intervention on the improvement of the serum/plasma and host cells (adipocytes and macrophages) LDL-C, oxysterols , PSS levels in high LDL-C levels volunteers and in respective conditioned media from the host cells/BCa cell lines co-culture, and superiority of the PSS to placebo intervention on the improvement of the cholesterol panel levels involved in BCa tolerance of chemotherapy and metastatic progression, according also to the molecular and genetical pathways.
Because of the unknown effect of PSS on the oxysterols metabolism and of its consequent chemotherapy and anti-metastatic proprieties, the trial will be divided in two phases (I and II):
- In this pilot phase the investigators will explore the effects of PSS intervention in 10 volunteers, evaluate feasibility of study protocol (participant recruitment and retention), and changes in mean and SD in oxysterols /PSS concentrations making changes to dose and power calculations if necessary. If the intervention causes any noteworthy effect in oxysterols serum/blood levels and/or on host cell co-culture with BCa cells the study will continue to Phase II:
II. In this phase a further 40 volunteers will be enrolled in the study satisfying our power calculation prediction to observe an effect.
This randomized cross-over double blind clinical trial will be run mainly at the School of Food Science and Nutrition, of the University of Leeds (FS\&N). Each site will have a nominated principle investigator. This will be in collaboration with the NHS - Leeds Teaching Hospitals Trust (LTHT), the Leeds Institute of Biomedical \& Clinical Sciences of the Faculty of Medicine and Health of the University of Leeds (LIBACS) and the Department of Chemistry of the University of Oslo (DC).
At each step point (Day 56, day 84 and day 140), the following trial assessments and procedures will be taken:
- Weight measurement;
- Participants diary card checking;
- Adverse effects and safety;
- Blood Pressure;
- Food intervention compliance checking by asking participants to return yoghurt packages back to trial team and relative recordings;
- 24h dietary recall questionnaire interview;
- LDL-C, HDL-C, Total Cholesterol, Triglycerides, non-HDL-C blood concentration and HDL-C/LDL-C ratio measurement;
- Serum/plasma OHCs concentration measurement;
- Serum/plasma PSS concentration measurement;
- Medium LDL-C concentration measurement after host cells co-culture with breast cancer cell lines;
- Medium OHCs concentration measurement after host cells co-culture with breast cancer cell lines;
- Medium PSS concentration measurement after host cells co-culture with breast cancer cell lines;
- Adipocytes, macrophages and breast cancer cell lines cell lines OHCs content measurement;
- Migratory and chemoresistance properties of the breast cancer cell lines cell lines after host cells co-culture.
- Conditions
- Hypercholesterolemia, Breast Cancer, Obesity
- Being tested
- Cholesterol Reducing Strawberry Yogurt Drink (Tesco Ltd), Low Fat Strawberry Yogurt Drinks (Morrisons Ltd)
- Keywords
- oxysterol, breast cancer, phytosterols, cholesterol metabolism
- Medical subject headings
- Hypercholesterolemia, Breast Neoplasms, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Dietary Supplement: Low Fat Strawberry Yogurt Drinks (Morrisons Ltd) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Concentration of oxysterols using LC-MS/MS measurement of host cells in 50 subjects after placebo and after intervention.
Effect of phytosterols enriched foods consumption compared to placebo intervention on migratory and chemoresistance properties of breast cancer cell lines (MDA.MB.231, MDA.MB.468, MCF7 and T47D) when in co-culture with the host-cells collected in each step of the trial.
Measured: 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
Effect of phytosterols enriched foods consumption compared to placebo intervention on migratory and chemoresistance properties of breast cancer cell lines (MDA.MB.231, MDA.MB.468, MCF7 and T47D) when in co-culture with the host-cells collected in each step of the trial.
Changes in proteins expression of oxysterols target genes.
Measured: 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
Effect of phytosterols enriched foods consumption compared to placebo intervention on migratory and chemoresistance properties of breast cancer cell lines (MDA.MB.231, MDA.MB.468, MCF7 and T47D) when in co-culture with the host-cells collected in each step of the trial.
Changes in gene expression of oxysterols target genes.
Measured: 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
Study of the effect of phytosterols on LDL-C concentration in 50 subjects after placebo and after intervention using Alere Afinion™.
Measured: 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
Study of the effect of phytosterols on HDL-C concentration in 50 subjects after placebo and after intervention using Alere Afinion™.
Measured: 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 Total Cholesterol
Study of the effect of phytosterols on Total Cholesterol concentration in 50 subjects after placebo and after intervention using Alere Afinion™.
Measured: 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 Triglycerides
Study of the effect of phytosterols on Triglycerides concentration in 50 subjects after placebo and after intervention using Alere Afinion™.
Measured: 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 non-HDL-C
Study of the effect of phytosterols on non-HDL-C concentration in 50 subjects after placebo and after intervention using Alere Afinion™.
Measured: Serum/plasma phytosterols and lipid concentrations will be measured during all the steps of the trial (baseline, 8th week, 12nd week, 20th week)
Quantify phytosterols in blood samples from volunteers.
Phytosterols panel serum/plasma levels after phytosterols enriched food or placebo intervention during all the steps of the trial.
Measured: Serum/plasma phytosterols and lipid concentrations will be measured during all the steps of the trial (baseline, 8th week, 12nd week, 20th week)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2019
- Study start10 Feb 2020
- Primary completion31 Dec 2021 (estimated)
- Study completion31 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypercholesterolemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 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.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Leeds
- Sponsor type
- University, hospital or other
- Collaborators
- The Leeds Teaching Hospitals NHS Trust, University of Oslo
- Responsible party
- Principal investigator, James Thorne, University of Leeds
- Investigators
- James L Thorne, PhD, Principal investigator, University of Leeds
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04147767
- Sponsor's protocol ID
- RD19/123502
- Acronym
- PINC
- Status last verified
- May 2021
- First submitted
- 21 Oct 2019
- Last updated
- 20 May 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be published in scientific journals, which will depend on the outcome of data analysis. Anonymized research data will be deposited with the University of Leeds data repository.
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised Control Cross-over Trial to Test How Dietary Plant Sterols Modify Tumour Promoting Capabilities of Non-tumour Host Cells in Volunteers With Elevated LDL-C
- ClinicalTrials.gov ID
- NCT04147767
- Acronym / sponsor ID
- PINC / RD19/123502
- Conditions
- Hypercholesterolemia, Breast Cancer, Obesity
- Keywords
- oxysterol, breast cancer, phytosterols, cholesterol metabolism
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of LeedsUniversity, hospital or other
- Collaborators
- The Leeds Teaching Hospitals NHS Trust, University of Oslo
- Study start
- 10 Feb 2020 (actual)
- Primary completion
- 31 Dec 2021 (estimated)
- Study completion
- 31 Dec 2021 (estimated)
- First posted
- 1 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Delivery of cholesterol to extra-hepatic tissues by LDL has a profound impact on different host cell types, many of which themselves have been implicated in BCa metastasis and chemoresistance.
Despite accumulating data, it is still unknown how host-cells help breast tumours metastasise or evade chemotherapy. The molecular link between cholesterol and metastasis may involve the enzymatic hydroxylation (an intermediate step in bile acid synthesis) of cholesterol. The synthesis and secretion of oxysterols into the tumour microenvironment and this is exacerbated in individuals with elevated LDL-cholesterol. This process, occurring largely in macrophages, adipocytes and fibroblasts, leads to biosynthesis and cellular export of oxysterols , which drive DNA mutations through oxidative stress, confer resistance to chemotherapy, enhance BCa growth and metastasis, and are elevated in serum of BCa patients at metastatic relapse. Our pilot data show non-cancer host-cells activate oxysterols signalling and drug resistance protein expression and confer chemotherapy resistance in adjacent cancer cells.
The investigators therefore propose to test the hypothesis that the reason epidemiological and clinical studies find elevated LDL-C and its co-morbidities associate with worse survival in BCa patients, is because the host-cells of these patients have enhanced cholesterol metabolic flux leading to increased oxysterols production and improved tolerance of chemotherapy and promotion of cancer metastatic pathways.
This trial is a multicentre cross-over double blind clinical trial in which volunteers with LDL-C ≥160mg/dL (4.1 mmol/L), recruited at the University of Leeds and/or identified through Horizon 2020 project PATHWAY-27, will be randomised into two arms of intervention, Group A (experimental arm) will be given an yoghurt drink enriched with PSS and Group B (placebo comparator) will be given yoghurt drink non-enriched with PSS. Each dietary intervention will last for 8 weeks, alternated with a 4 weeks of wash out period. This trial wants to highlight the superiority of the PSS (yoghurt drink enriched) to placebo (yoghurt drink non-enriched) intervention on the improvement of the serum/plasma and host cells (adipocytes and macrophages) LDL-C, oxysterols , PSS levels in high LDL-C levels volunteers and in respective conditioned media from the host cells/BCa cell lines co-culture, and superiority of the PSS to placebo intervention on the improvement of the cholesterol panel levels involved in BCa tolerance of chemotherapy and metastatic progression, according also to the molecular and genetical pathways.
Because of the unknown effect of PSS on the oxysterols metabolism and of its consequent chemotherapy and anti-metastatic proprieties, the trial will be divided in two phases (I and II):
- In this pilot phase the investigators will explore the effects of PSS intervention in 10 volunteers, evaluate feasibility of study protocol (participant recruitment and retention), and changes in mean and SD in oxysterols /PSS concentrations making changes to dose and power calculations if necessary. If the intervention causes any noteworthy effect in oxysterols serum/blood levels and/or on host cell co-culture with BCa cells the study will continue to Phase II:
II. In this phase a further 40 volunteers will be enrolled in the study satisfying our power calculation prediction to observe an effect.
This randomized cross-over double blind clinical trial will be run mainly at the School of Food Science and Nutrition, of the University of Leeds (FS\&N). Each site will have a nominated principle investigator. This will be in collaboration with the NHS - Leeds Teaching Hospitals Trust (LTHT), the Leeds Institute of Biomedical \& Clinical Sciences of the Faculty of Medicine and Health of the University of Leeds (LIBACS) and the Department of Chemistry of the University of Oslo (DC).
At each step point (Day 56, day 84 and day 140), the following trial assessments and procedures will be taken:
- Weight measurement;
- Participants diary card checking;
- Adverse effects and safety;
- Blood Pressure;
- Food intervention compliance checking by asking participants to return yoghurt packages back to trial team and relative recordings;
- 24h dietary recall questionnaire interview;
- LDL-C, HDL-C, Total Cholesterol, Triglycerides, non-HDL-C blood concentration and HDL-C/LDL-C ratio measurement;
- Serum/plasma OHCs concentration measurement;
- Serum/plasma PSS concentration measurement;
- Medium LDL-C concentration measurement after host cells co-culture with breast cancer cell lines;
- Medium OHCs concentration measurement after host cells co-culture with breast cancer cell lines;
- Medium PSS concentration measurement after host cells co-culture with breast cancer cell lines;
- Adipocytes, macrophages and breast cancer cell lines cell lines OHCs content measurement;
- Migratory and chemoresistance properties of the breast cancer cell lines cell lines after host cells co-culture.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Phytosterols Arm | Experimental | Dietary Supplement: Cholesterol Reducing Strawberry Yogurt Drink (Tesco Ltd)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. |
| Placebo Arm | Placebo comparator | Dietary Supplement: Low Fat Strawberry Yogurt Drinks (Morrisons Ltd)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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (15 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cholesterol Reducing Strawberry Yogurt Drink (Tesco Ltd)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 | Dietary supplement | Phytosterols Arm |
| Low Fat Strawberry Yogurt Drinks (Morrisons Ltd)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. | Dietary supplement | Placebo Arm |
Primary outcome
To change circulating oxysterols levels after phytosterols intervention.
Time frame: Serum/plasma oxysterols concentrations will be measured during all the steps of the trial (baseline, 8th week, 12nd week, 20th week)
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.
9 secondary outcomes
Change intra-cellular adipocyte and macrophages oxysterols concentrations
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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 Total Cholesterol
Time frame: 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 Triglycerides
Time frame: 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 non-HDL-C
Time frame: Serum/plasma phytosterols and lipid concentrations will be measured during all the steps of the trial (baseline, 8th week, 12nd week, 20th week)
Quantify phytosterols in blood samples from volunteers.
Time frame: Serum/plasma phytosterols and lipid concentrations will be measured during all the steps of the trial (baseline, 8th week, 12nd week, 20th week)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2021.
- Individual participant dataSharing planned: Yes. Data will be published in scientific journals, which will depend on the outcome of data analysis. Anonymized research data will be deposited with the University of Leeds data repository.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James L Thorne, PhD principal investigator
University of Leeds
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cholesterol Reducing Strawberry Yogurt Drink (Tesco Ltd) and Low Fat Strawberry Yogurt Drinks (Morrisons Ltd) in people with Hypercholesterolemia and Breast Cancer, run by University of Leeds at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact James L Thorne, PhD (+440113343 0684, J.L.Thorne@leeds.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To change circulating oxysterols levels after phytosterols intervention. (time frame: Serum/plasma oxysterols concentrations will be measured during all the steps of the trial (baseline, 8th week, 12nd week, 20th week)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2021.