Clinical trial NCT06151015: The Combined Effect of Dietary Nitrate and Caloric Restriction on Cognitive and Vascular Function.
Official title: Testing the Combined Effect of Dietary Nitrate and Caloric Restriction on Cognitive and Vascular Function in Older Adults Living with Overweight or Obesity: a 28-Day Pilot Randomised Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Healthy
Older Adults
Overweight and Obesity
Lead sponsor: University of Nottingham
Sponsor class: OTHER
Collaborators: name: King Abdulaziz University
First posted: 2023-11-30
Enrollment: 20
Sex: ALL
Minimum age (years): 60
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Pilot, randomised, parallel trial
Primary purpose: PREVENTION

Brief summary: This pilot study will compare the effect of combining dietary nitrate and caloric restriction versus dietary nitrate alone. The participant will be contacted, having responded to an advertisement on social media and posters, to attend the screening visit. They will be asked about their health status, suitability for MRI and availability. The investigators will use physical activity and eating attitude questionnaires. The investigators will also measure their height, weight, body mass index (BMI), and blood pressure (BP) and undertake blood tests. If they are eligible, they will be randomised to one of the two arms. The first group will consume nitrate-rich beetroot juice with a calorie-restricted diet for 28 days. The second group will drink the same juice with a weight-maintenance diet for the same period. The food and drinks will be provided. The outcome measures will be measured twice (at the baseline and end visits) to evaluate the change. The primary outcome is the cognitive function. The secondary outcomes are peripheral vascular health (BP and microvascular perfusion), cerebral vascular health (brain blood flow), anthropometry, body composition, and exhaled NO and nitrate concentrations. Also, the feasibility and accessibility of the study will be assessed.

Detailed description: Twenty healthy males and females, aged 60-70 years, non-smokers, and living with overweight or obesity (BMI 25-40 kg/m2) will be recruited to a 28-day pilot, randomised, parallel trial to follow one of the interventions (dietary nitrate with calorie-restricted diet or dietary nitrate with weight-maintenance diet) if they are eligible. Their energy requirement will be calculated using the Mifflin-St Jeor Equation, and the participant will be instructed to follow a healthy diet ( pre-diet standardisation) for three days before the intervention to minimise the effect of the sudden change of their habitual diet (during which their energy requirement will be met). At the Baseline Visit (Day 0), they will be randomised to one of the two arms, and the outcome measurements will be taken. Cognitive function will be measured via a pen-and-paper test (TMT) and a cognitive battery of tests (COMPASS). Clinic and home resting blood pressure (BP) will be measured using an automated BP monitor. Microvascular perfusion will be measured by a Laser Doppler monitor. Cerebral blood flow will be measured using a brain MRI scan. Height, weight, BMI, skinfold thickness, and waist circumference will be measured via a wall-mounted stadiometer, calibrated scale, BMI equation, calipers, and a tape measure, respectively. Body composition will be measured by a bioelectrical impedance analysis (BIA). Exhaled NO will be measured using a fractional exhaled nitric oxide analyser (FeNO). Blood samples will be taken to measure plasma nitrate concentrations. Physical activity will be monitored through a wearable smartwatch with an integrated accelerometer. The participants will be provided with 14 bottles of nitrate-rich beetroot juice (70 ml, which provides 6.5mmol of nitrate/day) with their allocated diet to be consumed in the next 14 days, starting from the next day (Day 1), and the remaining 14 days' supply will be delivered on Day 13. There will be an energy deficit of 1,000 kcal/day if they are allocated to the caloric restriction group. Otherwise, the energy requirement will be met. After completing the 28-day intervention, the participant will attend the End Visit (Day 29), to repeat the same study measurements they have done in the Baseline Visit. An exit feedback questionnaire will be given to collect information on the acceptability and compliance with the measurement protocols and intervention.

Eligibility criteria: Inclusion Criteria:

* Participant is able to give written informed consent for their participation in the study.
* Healthy.
* Non-smoking adults.
* Male or female.
* Aged 60 to 75 years.
* BMI between 25 and 40 kg/m2.

Exclusion Criteria:

* Systolic BP \> 180mmHg and/or diastolic BP \>110mmHg at the Clinic Screening Visit.
* Contraindication for MRI.
* Does not have adequate understanding of verbal and written information in English, sufficient to complete an MRI safety screening and to give informed consent.
* Any existing or previous medical condition that may affect the study outcomes (i.e., diabetes, kidney dysfunction, malignant cancer, brain surgery, stroke).
* Any medical treatment that may affect the study outcomes (i.e., diuretics, anti-acids, organic nitrates, anti-pyschotics or neuro-stimulants).
* Evidence of an eating disorder as indicated by the Three-factor eating questionnaire (Eating Attitudes Tests-26).
* Blood donation within the last 3 months of the anticipated intervention beginnings.
* Having taken part in a research study in the last 3 months involving invasive procedures or an inconvenience allowance.
* High-alcohol consumers (≥ 14 units/week for females, and ≥ 22 units/week for males).
* Vegetarianism (likely to have very high nitrate intake and food provided during the dietary intervention unsuitable).
* Weight change over 3.0kg in the last 2 months (important influence on vascular function).

Primary outcomes:
measure: Cognitive function (TMT-B)
timeFrame: Baseline Visit (Day 0)-one day before intervention, and End Visit (Day 29)-one day after intervention.
Secondary outcomes:
measure: Composite score of cognitive function
timeFrame: Baseline Visit (Day 0)-one day before intervention, and End Visit (Day 29)-one day after intervention.
measure: Cognitive function individual tasks (alphabetic working memory)
timeFrame: Baseline Visit (Day 0)-one day before intervention, and End Visit (Day 29)-one day after intervention.
measure: Cognitive function individual task (serial subtraction)
timeFrame: Baseline Visit (Day 0)-one day before intervention, and End Visit (Day 29)-one day after intervention.
measure: Cognitive function individual task (stroop)
timeFrame: Baseline Visit (Day 0)-one day before intervention, and End Visit (Day 29)-one day after intervention.
measure: Cognitive function individual task (peg and ball)
timeFrame: Baseline Visit (Day 0)-one day before intervention, and End Visit (Day 29)-one day after intervention.
measure: Cognitive function individual task (simple reaction time)
timeFrame: Baseline Visit (Day 0)-one day before intervention, and End Visit (Day 29)-one day after intervention.
measure: Cognitive function (TMT-A)
timeFrame: Baseline Visit (Day 0)-one day before intervention, and End Visit (Day 29)-one day after intervention.
measure: Clinic blood pressure for systolic and diastolic pressure
timeFrame: Baseline Visit (Day 0)-one day before intervention, and End Visit (Day 29)-one day after intervention.
measure: Continuous home blood pressure for systolic and diastolic pressure
timeFrame: Every three days starting from Day 1 until Day 28 of the intervention.
measure: Microvascular perfusion
timeFrame: Baseline Visit (Day 0)-one day before intervention, and End Visit (Day 29)-one day after intervention.
measure: Cerebral blood flow
timeFrame: Baseline Visit (Day 0)-one day before intervention, and End Visit (Day 29)-one day after intervention.
measure: Anthropometry (weight)
timeFrame: Baseline Visit (Day 0)-one day before intervention, and End Visit (Day 29)-one day after intervention.
measure: Anthropometry (BMI)
timeFrame: Baseline Visit (Day 0)-one day before intervention, and End Visit (Day 29)-one day after intervention.
measure: Anthropometry (skinfold thickness)
timeFrame: Baseline Visit (Day 0)-one day before intervention, and End Visit (Day 29)-one day after intervention.
measure: Anthropometry (waist circumference)
timeFrame: Baseline Visit (Day 0)-one day before intervention, and End Visit (Day 29)-one day after intervention.
measure: Body composition (fat mass)
timeFrame: Baseline Visit (Day 0)-one day before intervention, and End Visit (Day 29)-one day after intervention.
measure: Body composition (fat-free mass)
timeFrame: Baseline Visit (Day 0)-one day before intervention, and End Visit (Day 29)-one day after intervention.
measure: Exhaled nitric oxide
timeFrame: Baseline Visit (Day 0)-one day before intervention, and End Visit (Day 29)-one day after intervention.
measure: Nitrate concentrations
timeFrame: Baseline Visit (Day 0)-one day before intervention, and End Visit (Day 29)-one day after intervention.
measure: Feasibility and accessibility
timeFrame: End Visit (Day 29).
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: The University of Nottingham
state: Nottinghamshire
Study officials:
affiliation: University of Nottingham
name: Moira A Taylor, PhD RD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Alharbi M, Stephan BC, Shannon OM, Siervo M. Does dietary nitrate boost the effects of caloric restriction on brain health? Potential physiological mechanisms and implications for future research. Nutr Metab (Lond). 2023 Oct 25;20(1):45. doi: 10.1186/s12986-023-00766-9.
citation: Alharbi M, Chiurazzi M, Nasti G, Muscariello E, Mastantuono T, Koechl C, Stephan BC, Shannon OM, Colantuoni A, Siervo M. Caloric Restriction (CR) Plus High-Nitrate Beetroot Juice Does Not Amplify CR-Induced Metabolic Adaptation and Improves Vascular and Cognitive Functions in Overweight Adults: A 14-Day Pilot Randomised Trial. Nutrients. 2023 Feb 10;15(4):890. doi: 10.3390/nu15040890.
citation: Babateen AM, Shannon OM, O'Brien GM, Olgacer D, Koehl C, Fostier W, Mathers JC, Siervo M. Moderate doses of dietary nitrate elicit greater effects on blood pressure and endothelial function than a high dose: A 13-week pilot study. Nutr Metab Cardiovasc Dis. 2023 Jun;33(6):1263-1267. doi: 10.1016/j.numecd.2023.02.024. Epub 2023 Mar 2.
citation: Shannon OM, Gregory S, Siervo M. Dietary nitrate, aging and brain health: the latest evidence. Curr Opin Clin Nutr Metab Care. 2022 Nov 1;25(6):393-400. doi: 10.1097/MCO.0000000000000866. Epub 2022 Aug 9.
citation: Siervo M, Babateen A, Alharbi M, Stephan B, Shannon O. Dietary nitrate and brain health. Too much ado about nothing or a solution for dementia prevention? Br J Nutr. 2022 Sep 28;128(6):1130-1136. doi: 10.1017/S0007114522002434.
citation: Babateen AM, Shannon OM, O'Brien GM, Okello E, Smith E, Olgacer D, Koehl C, Fostier W, Wightman E, Kennedy D, Mathers JC, Siervo M. Incremental Doses of Nitrate-Rich Beetroot Juice Do Not Modify Cognitive Function and Cerebral Blood Flow in Overweight and Obese Older Adults: A 13-Week Pilot Randomised Clinical Trial. Nutrients. 2022 Mar 2;14(5):1052. doi: 10.3390/nu14051052.
citation: Siervo M, Arnold R, Wells JC, Tagliabue A, Colantuoni A, Albanese E, Brayne C, Stephan BC. Intentional weight loss in overweight and obese individuals and cognitive function: a systematic review and meta-analysis. Obes Rev. 2011 Nov;12(11):968-83. doi: 10.1111/j.1467-789X.2011.00903.x. Epub 2011 Jul 18.