Clinical trial NCT03944226: Is Dietary Nitrate Effective in Reducing Aerobic Glycolysis in Breast Cancer?
Official title: Is Dietary Nitrate Effective in Reducing Aerobic Glycolysis (AG) in Breast Cancer? - A Longitudinal Study Using Specialist Magnetic Resonance (MR) Methods
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Malignant Breast Tissue Neoplasm
Keywords: Beetroot juice
Magnetic Resonance Imaging
Breast cancer
Lead sponsor: University of Aberdeen
Sponsor class: OTHER
Collaborators: name: NHS Grampian
First posted: 2019-05-09
Enrollment: 16
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single Group: trials with a single arm
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Baseline: Lipid composition in tumour
timeFrame: Scan one day before intervention (Day 0)
measure: Post intervention: Lipid composition in tumour
timeFrame: Scan one day after completion of intervention (Day 6)
measure: Baseline: Lipid composition in whole breast tissue surrounding tumour
timeFrame: Scan one day before intervention (Day 0)
measure: Post intervention: Lipid composition in whole breast tissue surrounding tumour
timeFrame: Scan one day after completion of intervention (Day 6)
measure: Baseline: Water displacement in tumour
timeFrame: Scan one day before intervention (Day 0)
measure: Post intervention: Water displacement in tumour
timeFrame: Scan one day after completion of intervention (Day 6)
Secondary outcomes:
Other outcomes:
Locations:
city: Aberdeen
country: United Kingdom
facility: Aberdeen Biomedical Imaging Centre
Study officials:
affiliation: University of Aberdeen
name: Jiabao He, PhD
role: STUDY_CHAIR
affiliation: University of Aberdeen
name: Vasiliki Mallikourti, MSc
role: PRINCIPAL_INVESTIGATOR
References:
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citation: 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.
citation: 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.