Clinical trial NCT02907684: The Impact of Almond Nut Consumption on Markers of CVD & Metabolic Health
Official title: A Randomised, Controlled Parallel Dietary Intervention to Investigate the Effect of Almond Snack Consumption on Cardio-metabolic Disease Risk Markers Compared With Isocaloric Snacks, in Adults at Moderate Risk of Cardiovascular Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiovascular Disease
Keywords: Cardiovascular disease
Non alcoholic fatty liver
Diabetes
Almonds
Endothelium-dependent vasodilation
Fecal short chain fatty acids (SCFAs)
Snacking
Lead sponsor: King's College London
Sponsor class: OTHER
Collaborators: name: Almond Board of California
First posted: 2016-09-20
Enrollment: 108
Sex: ALL
Minimum age (years): 30
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this study is to investigate the cardio-metabolic health effects of consuming almond nuts in place of habitual (usual) snack products in adults at moderate risk of developing cardiovascular disease

Detailed description: Tree nuts are recommended in the prevention and management of cardiovascular disease (CVD) largely based on their LDL (low density lipoprotein) lowering effects, but the CVD risk reduction observed with tree nut consumption is greater than that predicted by their hypocholesterolemic effects alone. Other health benefits have also been noted by our group, such as moderation of postprandial lipemia , as well as by others such as modified postprandial glycemia , decreased blood pressure (BP) , improvement in oxidant status and weight loss. Robust evidence for the protective cardio-metabolic effects of nuts from the PREDIMED study has highlighted the association between nut consumption and decreased risk of cardiovascular events, obesity, metabolic syndrome and type 2 diabetes (T2DM). However, there is a paucity of evidence on the effects of almonds on vascular function in humans (BP and endothelium-dependent vasodilation (EDV)), although there is evidence that almonds promote nitric oxide (NO) release in animals consuming high-fat diets. Fundamental to vascular health is a well-functioning liver and there is increasing evidence to demonstrate that the accumulation of liver fat is a causative factor in the development of cardio-metabolic disorders. Non-alcoholic fatty liver disease (NAFLD) is now considered the hepatic manifestation of the metabolic syndrome (MetS); recent data has shown that it is linked to increased CVD risk via direct effects on vascular function (and EDV) independently of obesity and MetS . NAFLD is thought to affect 30% of the population in developed countries, and up to two-thirds of people with obesity and 50% of people with hyperlipidemia. Development of fatty liver, mainly attributable to obesity and elevated postprandial lipemia, is associated with increased inflammation, oxidative stress, insulin resistance, dyslipidemia and impaired EDV, and predicts risk of CVD and T2DM .

Therefore, the long-term goal of this research is to understand the mechanisms underpinning how dietary change can drive favourable modification of CVD disease risk and to identify patterns in population food choices, specifically almond consumption, that tend to correlate with reduced CVD disease risk. The primary aim of this proposal is to investigate, in a randomised controlled, parallel arm, 6-wk dietary intervention (n=100) whether replacing snacks based on refined carbohydrates and poor in micronutrients/non-nutrient bioactives (NNB) with nutrient/NNB-dense, whole almond snacks can influence liver fat content (a key metabolic driver of insulin resistance and vascular dysfunction, and a hallmark of metabolic syndrome) and EDV (brachial FMD being an independent predictor of CVD events, in addition to related biomarkers of cardio-metabolic disease risk. The snacks products provide participants with 20% of their energy requirements via either whole almonds or as muffins/crackers that have been designed to mimic the average UK snack.

Eligibility criteria: Inclusion Criteria:

Subjects will be male or female, aged between 30-70 years who regularly consume ≥2 snack products a day. A principal aim is to identify and recruit subjects with increased risk of CVD, in order to increase the sensitivity of the study subjects to dietary change. Subjects who are at above average risk for developing CVD (relative risk \>1.5) will be selected using a metabolic scoring system (scoring ≥2 points), adapted from the Framingham risk score system, as used previously by Chong et al. 2012. Subjects will give their own written informed consent.

Exclusion Criteria:

1. Non-snack consumers (assessed as subjects consuming \<2 snack products per day by a specific FFQ (food frequency questionnaire) at screening, adapted from the short Health Survey for England (2007) Eating Habits Questionnaire).
2. A reported history of myocardial infarction or cancer.
3. Being fitted with a heart pacemaker.
4. Presence of metal inside the body (implants, devices, shrapnel, metal particles in eyes from welding etc.). History of black-outs/epilepsy.
5. Diabetes mellitus (fasting plasma glucose \>7 mmol/L).
6. Chronic coronary, renal or bowel disease or history of cholestatic liver disease or pancreatitis.
7. Presence of gastrointestinal disorder or use of a drug, which is likely to alter gastrointestinal motility or nutrient absorption.
8. History of substance abuse or alcoholism (past history of alcohol intake \>60 units/men or 50 units/women).
9. Currently pregnant, planning pregnancy, breastfeeding or having had a baby in the last 12 months.
10. Allergy or intolerance to nuts.
11. Unwilling to follow the protocol and/or give informed consent.
12. Weight change of \> 3 kg in preceding 2 months. BMI \<18 kg/m2 (underweight) or \>40 kg/m2 (morbidly obese due to potential technical difficulties making FMD and ambulatory blood pressure (ABP) measurements).
13. Current smokers or individuals who quit smoking within the last 6 months.
14. Participation in other research trials involving dietary or drug intervention and/ or blood collection in the past 3 months.
15. Unable or unwilling to comply with study protocol.
16. The above criteria will be measured using the screening questionnaires and from physical (blood pressure, weight, height) and biochemical measurements (full lipid count, liver function test, full blood count, glucose and insulin) made during the screening visit. Participant eligibility will be assessed against the inclusion/exclusion criteria and 'fitness' to participate will be assessed and signed off by a clinician.

Primary outcomes:
measure: Endothelium-dependent vasodilation
timeFrame: Baseline (week 2)
measure: Endothelium-dependent vasodilation
timeFrame: Week 8 (after 2 week run in)
measure: Liver fat %
timeFrame: Baseline (week 2)
measure: Liver fat %
timeFrame: Week 8 (after 2 week run in)
Secondary outcomes:
measure: Pancreatic fat
timeFrame: Baseline (week 2)
measure: Abdominal fat
timeFrame: Baseline (week 2)
measure: Muscle fat
timeFrame: Baseline (week 2)
measure: Pancreatic fat
timeFrame: Week 8 (after 2 week run in)
measure: Abdominal fat
timeFrame: Week 8 (after 2 week run in)
measure: Muscle fat
timeFrame: Week 8 (after 2 week run in)
measure: Body composition: body weight
timeFrame: Week 0, prior to 2 week run in
measure: Body composition: body weight
timeFrame: Week 2 'Baseline'
measure: Body composition: body weight
timeFrame: Week 4
measure: Body composition: body weight
timeFrame: Week 6
measure: Body composition: body weight
timeFrame: Week 8
measure: Body composition: body mass index
timeFrame: Week 0, prior to 2 week run in
measure: Body composition: body mass index
timeFrame: Week 2 'baseline'
measure: Body composition: body mass index
timeFrame: Week 4
measure: Body composition: body mass index
timeFrame: Week 6
measure: Body composition: body mass index
timeFrame: Week 8
measure: Body composition: Waist circumference
timeFrame: Week 0, prior to 2 week run in
measure: Body composition: Waist circumference
timeFrame: Week 2 'baseline'
measure: Body composition: Waist circumference
timeFrame: Week 4
measure: Body composition: Waist circumference
timeFrame: Week 6
measure: Body composition: Waist circumference
timeFrame: Week 8
measure: Body composition: Hip circumference
timeFrame: Week 0 (prior to 2 week run in)
measure: Body composition: Hip circumference
timeFrame: Week 2 'baseline'
measure: Body composition: Hip circumference
timeFrame: Week 4
measure: Body composition: Hip circumference
timeFrame: Week 6
measure: Body composition: Hip circumference
timeFrame: Week 8
measure: Blood pressure
timeFrame: Week 0 (prior to 2 week run in)
measure: Blood pressure
timeFrame: Week 2 'baseline'
measure: Blood pressure
timeFrame: Week 4
measure: Blood pressure
timeFrame: Week 6
measure: Blood pressure
timeFrame: Week 8
measure: 24 hour ambulatory blood pressure
timeFrame: Week 2 'Baseline
measure: 24 hour ambulatory blood pressure
timeFrame: Week 8
measure: 24 hour heart rate variability
timeFrame: Week 2 'baseline'
measure: 24 hour heart rate variability
timeFrame: Week 8
measure: Fecal short chain fatty acids
timeFrame: Week 2 'baseline
measure: Fecal short chain fatty acids
timeFrame: Week 8
measure: Gut microbiota
timeFrame: Week 2 'baseline'
measure: Gut microbiota
timeFrame: Week 8
measure: Fasting insulin
timeFrame: week 2 'baseline'
measure: Fasting insulin
timeFrame: week 8
measure: Fasting glucose
timeFrame: Week 2 'baseline'
measure: Fasting glucose
timeFrame: Week 8
measure: Fasting non esterified fatty acids (NEFA)
timeFrame: Week 2 'baseline'
measure: Fasting non esterified fatty acids (NEFA)
timeFrame: Week 8
measure: Plasma Total cholesterol
timeFrame: Week 2 'baseline
measure: Plasma Total cholesterol
timeFrame: Week 8
measure: Plasma LDL cholesterol
timeFrame: Week 2 'Baseline'
measure: Plasma LDL cholesterol
timeFrame: Week 8
measure: Plasma HDL cholesterol
timeFrame: Week 2 'Baseline'
measure: Plasma HDL cholesterol
timeFrame: Week 8
measure: Plasma HDL:LDL ratio
timeFrame: Week 2 'Baseline'
measure: Plasma HDL:LDL ratio
timeFrame: Week 8
measure: Plasma triglyceride concentration
timeFrame: Week 2 'baseline'
measure: Plasma triglyceride concentration
timeFrame: Week 8
measure: Homeostasis model assessment estimated insulin resistance (HOMA-IR)
timeFrame: Week 2 'Baseline'
measure: Homeostasis model assessment estimated insulin resistance (HOMA-IR)
timeFrame: Week 8
measure: Plasma adiponectin
timeFrame: Week 2 'Baseline'
measure: Plasma adiponectin
timeFrame: Week 8
measure: Plasma resistin
timeFrame: Week 2 'baseline'
measure: Plasma resistin
timeFrame: Week 8
measure: Plasma leptin
timeFrame: Week 2 'baseline'
measure: Plasma leptin
timeFrame: Week 8
Other outcomes:
measure: Adverse events
timeFrame: Through study completion, average of 1.5 years.
measure: Snack product acceptability
timeFrame: Week 6
measure: 4 day food diaries
timeFrame: 4 days at screening
measure: 4 day food diaries
timeFrame: 4 days at week 0 'Baseline'
measure: 4 day food diaries
timeFrame: 4 days at week 6
Locations:
city: London
country: United Kingdom
facility: King's College London, Diabetes and Nutritional Sciences Division
Study officials:
affiliation: King's College London
name: Sarah Berry, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: King's College London
name: Wendy Hall, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dikariyanto V, Smith L, Francis L, Robertson M, Kusaslan E, O'Callaghan-Latham M, Palanche C, D'Annibale M, Christodoulou D, Basty N, Whitcher B, Shuaib H, Charles-Edwards G, Chowienczyk PJ, Ellis PR, Berry SEE, Hall WL. Snacking on whole almonds for 6 weeks improves endothelial function and lowers LDL cholesterol but does not affect liver fat and other cardiometabolic risk factors in healthy adults: the ATTIS study, a randomized controlled trial. Am J Clin Nutr. 2020 Jun 1;111(6):1178-1189. doi: 10.1093/ajcn/nqaa100.