- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02907684
The Impact of Almond Nut Consumption on Markers of CVD & Metabolic Health (Almonds)
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 Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
-
London, United Kingdom, SE1 9NH
- King's College London, Diabetes and Nutritional Sciences Division
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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:
- 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).
- A reported history of myocardial infarction or cancer.
- Being fitted with a heart pacemaker.
- Presence of metal inside the body (implants, devices, shrapnel, metal particles in eyes from welding etc.). History of black-outs/epilepsy.
- Diabetes mellitus (fasting plasma glucose >7 mmol/L).
- Chronic coronary, renal or bowel disease or history of cholestatic liver disease or pancreatitis.
- Presence of gastrointestinal disorder or use of a drug, which is likely to alter gastrointestinal motility or nutrient absorption.
- History of substance abuse or alcoholism (past history of alcohol intake >60 units/men or 50 units/women).
- Currently pregnant, planning pregnancy, breastfeeding or having had a baby in the last 12 months.
- Allergy or intolerance to nuts.
- Unwilling to follow the protocol and/or give informed consent.
- 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).
- Current smokers or individuals who quit smoking within the last 6 months.
- Participation in other research trials involving dietary or drug intervention and/ or blood collection in the past 3 months.
- Unable or unwilling to comply with study protocol.
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: DIAGNOSTIC
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: SINGLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Almonds
Almond snacks
|
Participants to consume almonds as snacks to contribute to 20% of their energy requirements daily for 4 weeks
|
Placebo Comparator: Control muffins/crackers
Muffin/Cracker snacks
|
Participants to consume muffins/crackers as snacks to contribute to 20% of their energy requirements daily for 4 weeks NB all participants will have a run in period for 2 weeks whereby muffins are consumed, this is prior to randomisation. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Endothelium-dependent vasodilation
Time Frame: Baseline (week 2)
|
Measured via flow mediated dilation (FMD)
|
Baseline (week 2)
|
Endothelium-dependent vasodilation
Time Frame: Week 8 (after 2 week run in)
|
Measured via flow mediated dilation (FMD)
|
Week 8 (after 2 week run in)
|
Liver fat %
Time Frame: Baseline (week 2)
|
Via MRI and magnetic resonance spectroscopy (MRS) analysis.
Only a subset of 48 participants with aim of 20 per each arm to complete
|
Baseline (week 2)
|
Liver fat %
Time Frame: Week 8 (after 2 week run in)
|
Via MRI and MRS analysis.
Only a subset of 48 participants with aim of 20 per each arm to complete
|
Week 8 (after 2 week run in)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pancreatic fat
Time Frame: Baseline (week 2)
|
Via body MRI.
Only a subset of 48 participants with aim of 20 per each arm to complete.
|
Baseline (week 2)
|
Abdominal fat
Time Frame: Baseline (week 2)
|
Via body MRI.
Only a subset of 48 participants with aim of 20 per each arm to complete.
|
Baseline (week 2)
|
Muscle fat
Time Frame: Baseline (week 2)
|
Single measurement via body MRI.
Only a subset of 48 participants with aim of 20 per each arm to complete.Muscle fat will be measured in the soleus muscle in the lower calf.
|
Baseline (week 2)
|
Pancreatic fat
Time Frame: Week 8 (after 2 week run in)
|
Single measurement via body MRI.
Only a subset of 48 participants with aim of 20 per each arm to complete.
|
Week 8 (after 2 week run in)
|
Abdominal fat
Time Frame: Week 8 (after 2 week run in)
|
Single measurement via body MRI.
Only a subset of 48 participants with aim of 20 per each arm to complete.
|
Week 8 (after 2 week run in)
|
Muscle fat
Time Frame: Week 8 (after 2 week run in)
|
Single measurement via body MRI.
Only a subset of 48 participants with aim of 20 per each arm to complete.
Muscle fat will be measured in the soleus muscle in the lower calf.
|
Week 8 (after 2 week run in)
|
Body composition: body weight
Time Frame: Week 0, prior to 2 week run in
|
Using Tanita scales
|
Week 0, prior to 2 week run in
|
Body composition: body weight
Time Frame: Week 2 'Baseline'
|
Using Tanita scales
|
Week 2 'Baseline'
|
Body composition: body weight
Time Frame: Week 4
|
Using Tanita scales
|
Week 4
|
Body composition: body weight
Time Frame: Week 6
|
Using Tanita scales
|
Week 6
|
Body composition: body weight
Time Frame: Week 8
|
Using Tanita scales
|
Week 8
|
Body composition: body mass index
Time Frame: Week 0, prior to 2 week run in
|
Week 0, prior to 2 week run in
|
|
Body composition: body mass index
Time Frame: Week 2 'baseline'
|
Week 2 'baseline'
|
|
Body composition: body mass index
Time Frame: Week 4
|
Week 4
|
|
Body composition: body mass index
Time Frame: Week 6
|
Week 6
|
|
Body composition: body mass index
Time Frame: Week 8
|
Week 8
|
|
Body composition: Waist circumference
Time Frame: Week 0, prior to 2 week run in
|
Week 0, prior to 2 week run in
|
|
Body composition: Waist circumference
Time Frame: Week 2 'baseline'
|
Week 2 'baseline'
|
|
Body composition: Waist circumference
Time Frame: Week 4
|
Week 4
|
|
Body composition: Waist circumference
Time Frame: Week 6
|
Week 6
|
|
Body composition: Waist circumference
Time Frame: Week 8
|
Week 8
|
|
Body composition: Hip circumference
Time Frame: Week 0 (prior to 2 week run in)
|
Week 0 (prior to 2 week run in)
|
|
Body composition: Hip circumference
Time Frame: Week 2 'baseline'
|
Week 2 'baseline'
|
|
Body composition: Hip circumference
Time Frame: Week 4
|
Week 4
|
|
Body composition: Hip circumference
Time Frame: Week 6
|
Week 6
|
|
Body composition: Hip circumference
Time Frame: Week 8
|
Week 8
|
|
Blood pressure
Time Frame: Week 0 (prior to 2 week run in)
|
Week 0 (prior to 2 week run in)
|
|
Blood pressure
Time Frame: Week 2 'baseline'
|
Week 2 'baseline'
|
|
Blood pressure
Time Frame: Week 4
|
Week 4
|
|
Blood pressure
Time Frame: Week 6
|
Week 6
|
|
Blood pressure
Time Frame: Week 8
|
Week 8
|
|
24 hour ambulatory blood pressure
Time Frame: Week 2 'Baseline
|
Week 2 'Baseline
|
|
24 hour ambulatory blood pressure
Time Frame: Week 8
|
Week 8
|
|
24 hour heart rate variability
Time Frame: Week 2 'baseline'
|
Week 2 'baseline'
|
|
24 hour heart rate variability
Time Frame: Week 8
|
Week 8
|
|
Fecal short chain fatty acids
Time Frame: Week 2 'baseline
|
Subset of participants, n=30
|
Week 2 'baseline
|
Fecal short chain fatty acids
Time Frame: Week 8
|
Subset of participants, n=30
|
Week 8
|
Gut microbiota
Time Frame: Week 2 'baseline'
|
Subset of participants, n=30
|
Week 2 'baseline'
|
Gut microbiota
Time Frame: Week 8
|
Subset of participants, n=30
|
Week 8
|
Fasting insulin
Time Frame: week 2 'baseline'
|
week 2 'baseline'
|
|
Fasting insulin
Time Frame: week 8
|
week 8
|
|
Fasting glucose
Time Frame: Week 2 'baseline'
|
Week 2 'baseline'
|
|
Fasting glucose
Time Frame: Week 8
|
Week 8
|
|
Fasting non esterified fatty acids (NEFA)
Time Frame: Week 2 'baseline'
|
Week 2 'baseline'
|
|
Fasting non esterified fatty acids (NEFA)
Time Frame: Week 8
|
Week 8
|
|
Plasma Total cholesterol
Time Frame: Week 2 'baseline
|
Fasting
|
Week 2 'baseline
|
Plasma Total cholesterol
Time Frame: Week 8
|
Fasting
|
Week 8
|
Plasma LDL cholesterol
Time Frame: Week 2 'Baseline'
|
Fasting
|
Week 2 'Baseline'
|
Plasma LDL cholesterol
Time Frame: Week 8
|
Fasting
|
Week 8
|
Plasma HDL cholesterol
Time Frame: Week 2 'Baseline'
|
Fasting
|
Week 2 'Baseline'
|
Plasma HDL cholesterol
Time Frame: Week 8
|
Fasting
|
Week 8
|
Plasma HDL:LDL ratio
Time Frame: Week 2 'Baseline'
|
Fasting
|
Week 2 'Baseline'
|
Plasma HDL:LDL ratio
Time Frame: Week 8
|
Fasting
|
Week 8
|
Plasma triglyceride concentration
Time Frame: Week 2 'baseline'
|
Fasting
|
Week 2 'baseline'
|
Plasma triglyceride concentration
Time Frame: Week 8
|
Fasting
|
Week 8
|
Homeostasis model assessment estimated insulin resistance (HOMA-IR)
Time Frame: Week 2 'Baseline'
|
Fasting (calculated from insulin and glucose)
|
Week 2 'Baseline'
|
Homeostasis model assessment estimated insulin resistance (HOMA-IR)
Time Frame: Week 8
|
Fasting (calculated from insulin and glucose)
|
Week 8
|
Plasma adiponectin
Time Frame: Week 2 'Baseline'
|
Week 2 'Baseline'
|
|
Plasma adiponectin
Time Frame: Week 8
|
Week 8
|
|
Plasma resistin
Time Frame: Week 2 'baseline'
|
Week 2 'baseline'
|
|
Plasma resistin
Time Frame: Week 8
|
Week 8
|
|
Plasma leptin
Time Frame: Week 2 'baseline'
|
Week 2 'baseline'
|
|
Plasma leptin
Time Frame: Week 8
|
Week 8
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adverse events
Time Frame: Through study completion, average of 1.5 years.
|
Through study completion, average of 1.5 years.
|
|
Snack product acceptability
Time Frame: Week 6
|
Questionnaire for participants to rate acceptability including self-rated enjoyment, sensory aspects, gastrointestinal effects, palatability, and appetite sensations, and likelihood that they will continue to consume the almonds/muffins as a snack after the study has ended
|
Week 6
|
4 day food diaries
Time Frame: 4 days at screening
|
4 days at screening
|
|
4 day food diaries
Time Frame: 4 days at week 0 'Baseline'
|
4 days at week 0 'Baseline'
|
|
4 day food diaries
Time Frame: 4 days at week 6
|
4 days at week 6
|
Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- ABC RFP-DHW001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cardiovascular Disease
-
University of FloridaUniversity of Alabama at Birmingham; Brown UniversityCompletedCardiovascular Disease | Psychosocial Influence on Cardiovascular DiseaseUnited States
-
National Heart, Lung, and Blood Institute (NHLBI)CompletedCardiovascular Disease | Inflammatory DiseaseUnited States
-
VA Office of Research and DevelopmentNot yet recruitingCardiovascular DiseaseUnited States
-
Baptist Health South FloridaUniversity of California, Los Angeles; Quest Diagnostics-Nichols InsituteActive, not recruitingCardiovascular DiseaseUnited States
-
Laval UniversityActive, not recruitingCardiovascular DiseaseCanada
-
Penn State UniversityCalifornia Healthcare InstituteCompleted
-
Penn State UniversityAlmond Board of California; The Hershey CompanyCompletedCardiovascular DiseaseUnited States
-
VA Office of Research and DevelopmentCompleted
-
Aziyo Biologics, Inc.CompletedCardiovascular DiseaseUnited States
-
Monash UniversityCompletedCardiovascular DiseaseAustralia
Clinical Trials on Almonds
-
University of FloridaAlmond Board of CaliforniaCompleted
-
United States Department of Agriculture (USDA)Almond Board of CaliforniaCompleted
-
David BaerAlmond Board of CaliforniaCompletedHealthy | Focus: Effect of Processing on Energy Value of AlmondsUnited States
-
Boston UniversityTufts UniversityCompletedCoronary Artery DiseaseUnited States
-
Penn State UniversityAlmond Board of CaliforniaCompleted
-
University of California, DavisCompleted
-
Diabetes Foundation, IndiaNational Diabetes Obesity and Cholesterol FoundationCompleted
-
Tufts UniversityCompletedMild Cognitive ImpairmentUnited States
-
Maastricht University Medical CenterAlmond Board of CaliforniaCompletedPreDiabetes | Overweight and Obesity | Impaired Glucose Tolerance | Impaired Fasting GlucoseNetherlands
-
Florida State UniversityAlmond Board of CaliforniaRecruiting