NCT05342012

Brief Summary

Type 2 diabetes mellitus (T2DM) is a metabolic condition characterized by chronic hyperglycemia and progressive insulin resistance, which progressively lead to macro- and microvascular damage. With the number of people with T2DM continuing to rise, this pandemic is expected to reach 700 million people by 2045, such that the costs associated with its clinical management are likely to become unsustainable. Therefore, identifying cost effective alternative interventions is imperative. Diets rich in fruits and vegetables are well known to have cardiovascular benefits and reduce the risk of getting T2DM. The beneficial effects of vegetables on cardiovascular outcomes are particularly effective in green leafy vegetables and beetroot. This may in part be due to a high concentration of inorganic nitrate, and its beneficial effects on cardiovascular health due to its effect on nitric oxide (NO•). Increased dietary nitrate intake elevates cyclic guanosine monophosphate \[(cGMP)\]. Importantly, cGMP has also been shown to increase brown fat expression by 'beiging' WAT in mice through an NO• dependent process. Recent developments in the ability to non-invasively measure BAT activation using magnetic resonance imaging (MRI) and infrared thermography (ITR) has opened the possibility to study the effects of nitrate on BAT activation in man. BAT depots in humans with T2DM have been identified using MRI but not yet with the more easily accessible technique of IRT. It is hypothesised that nitrate can increase BAT activation and quantity in people with T2DM.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
13

participants targeted

Target at below P25 for not_applicable diabetes-mellitus-type-2

Timeline
Completed

Started Jun 2022

Geographic Reach
1 country

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 1, 2022

Completed
2 months until next milestone

First Posted

Study publicly available on registry

April 22, 2022

Completed
2 months until next milestone

Study Start

First participant enrolled

June 30, 2022

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 31, 2023

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 31, 2023

Completed
Last Updated

October 10, 2023

Status Verified

October 1, 2023

Enrollment Period

7 months

First QC Date

March 1, 2022

Last Update Submit

October 9, 2023

Conditions

Diabetes Mellitus, Type 2

Keywords

BeetrootBrown Adipose TissueInfrared spectrometryMagnetic Resonance ImagingNitratesType II Diabetes Mellitus

Outcome Measures

Primary Outcomes (7)

  • MRI Imaging of Supraclavicular BAT

    High-resolution 3-dimensional T1-weighted imaging will be acquired using repetition time, echo time and field of view. All imaging sequences will have anatomical coverage of the neck, supraclavicular region and the apices of the lung.

    MRI on day 14 (Visit 2) before 60 minutes of cold exposure, following 14-days beetroot/placebo supplementation with 7-day washout between crossover.

  • MRI Imaging of Supraclavicular BAT

    High-resolution 3-dimensional T1-weighted imaging will be acquired using repetition time, echo time and field of view. All imaging sequences will have anatomical coverage of the neck, supraclavicular region and the apices of the lung.

    MRI on day 14 (Visit 2) following 60 minutes of cold exposure, following 14-days beetroot/placebo supplementation with 7-day washout between crossover.

  • MRI Imaging of Supraclavicular BAT

    High-resolution 3-dimensional T1-weighted imaging will be acquired using repetition time, echo time and field of view. All imaging sequences will have anatomical coverage of the neck, supraclavicular region and the apices of the lung.

    MRI on day 35 (visit 3) before 60 minutes of cold exposure, following 14-days beetroot/placebo supplementation with 7-day washout between crossover.

  • MRI Imaging of Supraclavicular BAT

    High-resolution 3-dimensional T1-weighted imaging will be acquired using repetition time, echo time and field of view. All imaging sequences will have anatomical coverage of the neck, supraclavicular region and the apices of the lung.

    MRI on day 35 (visit 3) following 60 minutes of cold exposure, following 14-days beetroot/placebo supplementation with 7-day washout between crossover.

  • A 3D multi-point Dixon sequence will be utilized for the water-fat imaging.

    A 3D multi-point Dixon sequence will be utilized for the water-fat imaging.

    At start of MRI Imaging of Supraclavicular BAT

  • A 3D multi-point Dixon sequence will be utilized for the water-fat imaging.

    A 3D multi-point Dixon sequence will be utilized for the water-fat imaging.

    At end of MRI Imaging of Supraclavicular BAT

  • Pixel wise quantification of fat fraction will be performed from fat and water maps.

    Pixel wise quantification of fat fraction will be performed from fat and water maps.

    At time of MRI Imaging

Secondary Outcomes (7)

  • IRT Imaging of Supraclavicular BAT

    IRT on day 14 (Visit 2) and day 35 (visit 3), before and after 60 minutes of cold water immersion, following 14-days beetroot/placebo supplementation with 7-day washout between crossover.

  • Biomarkers - Nitrate

    Blood sampling on day 14 (Visit 2) and day 35 (visit 3) following 14-days beetroot/placebo supplementation with 7-day washout between crossover.

  • Biomarkers - Nitrite

    Blood sampling on day 14 (Visit 2) and day 35 (visit 3) following 14-days beetroot/placebo supplementation with 7-day washout between crossover.

  • Biomarkers - cGMP

    Blood sampling on day 14 (Visit 2) and day 35 (visit 3) following 14-days beetroot/placebo supplementation with 7-day washout between crossover.

  • Biomarkers - Nitrate

    Blood sampling on day 14 (Visit 2) and day 35 (visit 3) following 14-days beetroot/placebo supplementation with 7-day washout between crossover.

  • +2 more secondary outcomes

Study Arms (2)

Experimental: Beetroot juice then nitrate depleted beetroot juice

EXPERIMENTAL

Participants will be asked to consume 140ml of beetroot juice prior to their first experimental visit. Participants will then be asked to consume 140ml a day for 2 weeks, and finally visit the investigators once more following another 140ml drink.

Dietary Supplement: Concentrated beetroot juiceDietary Supplement: Nitrate depleted beetroot juice

Experimental: Nitrate depleted beetroot juice then beetroot juice

EXPERIMENTAL

Participants will be asked to consume 140ml of placebo prior to their first experimental visit. Participants will then be asked to consume 140ml a day for 2 weeks, and finally visit the investigators once more following another 140ml drink.

Dietary Supplement: Concentrated beetroot juiceDietary Supplement: Nitrate depleted beetroot juice

Interventions

Concentrated beetroot juiceDIETARY_SUPPLEMENT

Acute and chronic supplementation of beetroot juice.

Experimental: Beetroot juice then nitrate depleted beetroot juiceExperimental: Nitrate depleted beetroot juice then beetroot juice
Nitrate depleted beetroot juiceDIETARY_SUPPLEMENT

(Nitrate depleted beetroot juice

Experimental: Beetroot juice then nitrate depleted beetroot juiceExperimental: Nitrate depleted beetroot juice then beetroot juice

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Males or women with Type 2 Diabetes Mellitus

You may not qualify if:

  • Individuals with a BMI over 30
  • Individuals with severe claustrophobia (this would make imaging the BAT less reliable)
  • Current smokers (or those that have smoked within 3 months)
  • Proton pump inhibitors or phosphodiesterase inhibitor users, as these may affect \[cGMP\]. Half life of this drug is short. Participants can choose to not use this if they wish to participate.
  • Individuals with any other serious medical condition which would interfere with data interpretation or safety will be excluded from participation.
  • Unable to give informed consent

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Bournemouth University

Bournemouth, Dorset, BH12 5BB, United Kingdom

Location

University of Portsmouth

Portsmouth, Hampshire, PO1 2UP, United Kingdom

Location

Southern Health NHS Foundation Trust

Southampton, Hampshire, SO40 8DX, United Kingdom

Location

Shore Medical

Poole, United Kingdom

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Study Officials

  • Rebecc Neal

    Senior Lecturer in Exercise Physiology

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
Double blind randomised control trial. Supplements will be dispensed by a member of the research team.
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 1, 2022

First Posted

April 22, 2022

Study Start

June 30, 2022

Primary Completion

January 31, 2023

Study Completion

July 31, 2023

Last Updated

October 10, 2023

Record last verified: 2023-10

Locations

GB(4)