Is Dietary Nitrate Effective in Reducing Aerobic Glycolysis in Breast Cancer? (BEET)

Is Dietary Nitrate Effective in Reducing Aerobic Glycolysis (AG) in Breast Cancer? - A Longitudinal Study Using Specialist Magnetic Resonance (MR) Methods

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.

Study Overview

• Status: Unknown
• Conditions: Malignant Breast Tissue Neoplasm
• Intervention / Treatment: Dietary supplement: Beetroot juice

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 16
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Vasiliki Mallikourti, MSc; Phone Number: +44 (0)1224 438351; Email: r02vm16@abdn.ac.uk
• Study Contact Backup: Name: Jiabao He, PhD; Phone Number: +44 (0)1224 43-7321; Email: jiabao.he@abdn.ac.uk

Study Locations

• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZD
    • Aberdeen Biomedical Imaging Centre
    • Contact: Vasiliki Mallikourti, MSc; Phone Number: +44 (0)1224 438351; Email: r02vm16@abdn.ac.uk
    • Principal Investigator: Vasiliki Mallikourti, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Dietary supplement: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline: Lipid composition in tumour	Lipid peak volume with units of ratio	Scan one day before intervention (Day 0)
Post intervention: Lipid composition in tumour	Lipid peak volume ratio with units of ratio	Scan one day after completion of intervention (Day 6)
Baseline: Lipid composition in whole breast tissue surrounding tumour	fat fraction with units of %	Scan one day before intervention (Day 0)
Post intervention: Lipid composition in whole breast tissue surrounding tumour	fat fraction with units of %	Scan one day after completion of intervention (Day 6)
Baseline: Water displacement in tumour	Water displacement with units of micrometer	Scan one day before intervention (Day 0)
Post intervention: Water displacement in tumour	Water displacement with units of micrometer	Scan one day after completion of intervention (Day 6)

Collaborators and Investigators

• Sponsor: University of Aberdeen
• Collaborators: NHS Grampian
• Investigators: Study Chair: Jiabao He, PhD, University of Aberdeen; Principal Investigator: Vasiliki Mallikourti, MSc, University of Aberdeen

Publications and helpful links

General Publications

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

Study record dates

Study Major Dates

• Study Start (Anticipated): May 13, 2019
• Primary Completion (Anticipated): April 26, 2020
• Study Completion (Anticipated): June 30, 2020

Study Registration Dates

• First Submitted: May 7, 2019
• First Submitted That Met QC Criteria: May 8, 2019
• First Posted (Actual): May 9, 2019

Study Record Updates

• Last Update Posted (Actual): May 14, 2019
• Last Update Submitted That Met QC Criteria: May 13, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Breast cancer; Magnetic Resonance Imaging; Beetroot juice
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 2-114-18; 17/049 (Other Grant/Funding Number: Research and Development Endowment Research Grants)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No