Is Dietary Nitrate Effective in Reducing Aerobic Glycolysis in Breast Cancer?

NCT ID: NCT03944226

Last Updated: 2019-05-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-05-13

Study Completion Date

2020-06-30

Brief Summary

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Breast cancer is the most prevalent cancer affecting women, with 1 in 8 women in the UK developing breast cancer in their life time. Chemotherapy drugs, currently used for locally advanced breast cancers, are associated with side effects while dietary supplements have complex effects with a relatively small effect size.

Breast tumours have different metabolism compared to healthy tissue, including elevated lactate production by aerobic glycolysis (AG), an underpinning feature of metabolism in breast cancer cells. Dietary nitrate, contained in leafy green vegetables and beetroot, has been shown to improve energy efficiency in exercising skeletal muscle, positioning itself as a disruptor of AG.

The purpose of this study is to examine if dietary nitrate can disrupt AG and as a result to halt or even reverse tumour progression and survival. This study will look at scans of breast tumours using magnetic resonance imaging (MRI). Changes to tumour related biochemical substances will be measured by advanced magnetic resonance spectroscopy and changes to tissue structure will be measured by advanced diffusion MRI techniques.

In this study, 16 patients undergoing surgery will be recruited for two MRI scans following a 5 day intervention programme.

Detailed Description

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In this longitudinal study, the investigators propose to examine the changes in lipid composition and microstructure in breast tumours at baseline and post dietary nitrate intervention through the applications of novel non-invasive magnetic resonance spectroscopy (MRS) methods and diffusion and lipid profiling MR imaging methods in patients. The investigators hypothesise that dietary nitrate disrupts tumour progression in breast cancer.

1. Is there a significant difference in lipid composition in the tumour measured by MRS between baseline and post dietary nitrate intervention?
2. Is there a significant difference in lipid composition in the whole breast tissue surrounding tumour measured by MRI between baseline and post dietary nitrate intervention?
3. Is there a significant difference in tissue microstructure measured by MRI between baseline and post dietary nitrate intervention in the breast tissue?

To assess the effect of dietary nitrate on tumour progression, paired t-tests will be performed on lipid composition measured from tumour between baseline and post intervention. To assess the effect of dietary nitrate on tumour progression, paired t-tests will be performed on lipid composition in the whole breast tissue surrounding tumour between baseline and post intervention. To assess the effect of dietary nitrate on tissue microstructure paired t-tests will be performed on water displacement measured from tumour between baseline and post intervention.

Conditions

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Malignant Breast Tissue Neoplasm

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Single Group: trials with a single arm
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Single group with no masking

Study Groups

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Beetroot

16 patients confirmed with a diagnosis of invasive ductal carcinoma who will undergo wide local excision surgery or mastectomy. All patients in the single arm will undergo a 5 day intervention drinking concentrated beetroot juice and 2 magnetic resonance imaging scan sessions pre and post intervention. MRI scan sessions will be composed of research scans including diffusion and lipid profiling MR imaging methods and MR spectroscopy (MRS) methods.

Group Type EXPERIMENTAL

Beetroot juice

Intervention Type DIETARY_SUPPLEMENT

The patient will follow a 5 day dietary nitrate intervention programme, taking 3 doses of 7cl (0.4 g nitrate per dose) concentrated beetroot juice (SPORT shot, James White Drinks, Suffolk, U.K.) a day.

Interventions

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Beetroot juice

The patient will follow a 5 day dietary nitrate intervention programme, taking 3 doses of 7cl (0.4 g nitrate per dose) concentrated beetroot juice (SPORT shot, James White Drinks, Suffolk, U.K.) a day.

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

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Inclusion Criteria

* Patients with pathologically confirmed invasive ductal carcinoma (Grade 2 or 3)
* Undergoing wide local excision surgery or mastectomy

Exclusion Criteria

* Started hormone or chemotherapy treatment before recruitment.
* Undergoing treatment for concurrent cancer diagnosis.
* Taking antibiotics, proton pump or vegetable dietary supplement.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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NHS Grampian

OTHER_GOV

Sponsor Role collaborator

University of Aberdeen

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jiabao He, PhD

Role: STUDY_CHAIR

University of Aberdeen

Vasiliki Mallikourti, MSc

Role: PRINCIPAL_INVESTIGATOR

University of Aberdeen

Locations

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Aberdeen Biomedical Imaging Centre

Aberdeen, , United Kingdom

Site Status

Countries

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United Kingdom

Central Contacts

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Vasiliki Mallikourti, MSc

Role: CONTACT

+44 (0)1224 438351

Jiabao He, PhD

Role: CONTACT

+44 (0)1224 43-7321

Facility Contacts

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Vasiliki Mallikourti, MSc

Role: primary

+44 (0)1224 438351

References

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Graham LJ, Shupe MP, Schneble EJ, Flynt FL, Clemenshaw MN, Kirkpatrick AD, Gallagher C, Nissan A, Henry L, Stojadinovic A, Peoples GE, Shumway NM. Current approaches and challenges in monitoring treatment responses in breast cancer. J Cancer. 2014 Jan 5;5(1):58-68. doi: 10.7150/jca.7047.

Reference Type BACKGROUND
PMID: 24396498 (View on PubMed)

Baker J, Ajani J, Scotte F, Winther D, Martin M, Aapro MS, von Minckwitz G. Docetaxel-related side effects and their management. Eur J Oncol Nurs. 2009 Feb;13(1):49-59. doi: 10.1016/j.ejon.2008.10.003. Epub 2009 Feb 7.

Reference Type BACKGROUND
PMID: 19201649 (View on PubMed)

Gatenby RA, Gillies RJ. Why do cancers have high aerobic glycolysis? Nat Rev Cancer. 2004 Nov;4(11):891-9. doi: 10.1038/nrc1478.

Reference Type BACKGROUND
PMID: 15516961 (View on PubMed)

Jones AM. Dietary nitrate supplementation and exercise performance. Sports Med. 2014 May;44 Suppl 1(Suppl 1):S35-45. doi: 10.1007/s40279-014-0149-y.

Reference Type BACKGROUND
PMID: 24791915 (View on PubMed)

McMahon NF, Leveritt MD, Pavey TG. The Effect of Dietary Nitrate Supplementation on Endurance Exercise Performance in Healthy Adults: A Systematic Review and Meta-Analysis. Sports Med. 2017 Apr;47(4):735-756. doi: 10.1007/s40279-016-0617-7.

Reference Type BACKGROUND
PMID: 27600147 (View on PubMed)

Bentley R, Gray SR, Schwarzbauer C, Dawson D, Frenneaux M, He J. Dietary nitrate reduces skeletal muscle oxygenation response to physical exercise: a quantitative muscle functional MRI study. Physiol Rep. 2014 Jul 22;2(7):e12089. doi: 10.14814/phy2.12089. Print 2014 Jul 1.

Reference Type BACKGROUND
PMID: 25052493 (View on PubMed)

Other Identifiers

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17/049

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2-114-18

Identifier Type: -

Identifier Source: org_study_id

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