Clinical trial NCT03419702: Almonds and Health Effects on Metabolism, Vascular Function and Cognition
Official title: Effects of Almond Consumption on Chronic Glucose Regulation, Vascular Function and Cognitive Performance: The AL-INCLUSIVE Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: PreDiabetes
Impaired Glucose Tolerance
Impaired Fasting Glucose
Overweight and Obesity
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: Almond Board of California
First posted: 2018-02-05
Enrollment: 43
Sex: ALL
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: SUPPORTIVE_CARE

Brief summary: The primary objective of the proposed study is to examine and understand the impact of long-term almond consumption on chronic glucose metabolism in subjects with impaired glucose tolerance and/or impaired fasting glucose.

Detailed description: Objectives:

Secondary objectives are to investigate if improved chronic glucose metabolism in subjects with impaired glucose tolerance and/or impaired fasting glucose after long-term almond consumption translates into improved peripheral and brain vascular function, and enhanced cognitive performance. In addition, the investigators will address to what extent improved chronic glucose metabolism in subjects with impaired glucose tolerance and/or impaired fasting glucose after long-term almond consumption can be explained by (combined) effects of lowered hepatic lipid accumulation and inflammation, skeletal muscle characteristics, visceral and subcutaneous fat accumulation, pancreatic function or fecal microbiota composition.

Study design:

The proposed study will be a 12 months randomised, controlled trial with a cross-over design. Two experimental periods of five months will be separated by a two months washout period.

Study population:

Forty-three impaired glucose tolerant and/or impaired fasting glucose subjects, with overweight and mild obesity (BMI 25-35 kg/m2), aged 40-70 years.

Intervention:

During the intervention period of 5 months, subjects will receive daily 50 gr almonds, but not in the 2 months washout and 5 months control periods.

Eligibility criteria: Inclusion Criteria:

* Aged between 40-70 years
* Men and women
* BMI between 25-35 kg/m2 (overweight and obese)
* Being classified as having impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG). IGT is defined according the criteria of the WHO and American Diabetes Association (ADA) as two-hour glucose concentrations of 7.8 to 11.0 mmol/l (140 to 199 mg per dL) during the 75-g oral glucose tolerance test. IFG is defined as having a fasting plasma glucose between 6.1 and 7.0 mmol/l (110 to 125 mg per dL) and a two-hour glucose concentration below 7.8 mmol/l (140 mg per dL).
* Serum total cholesterol \< 8.0 mmol/L (further testing is recommended for excessive hyperlipidemia \[serum total cholesterol ≥ 8.0 mmol/L\] according to the Standard for cardiovascular risk management of the Dutch general practitioners community \[NHG\])
* Serum triacylglycerol \< 4.52 mmol/L
* No current smoker
* No diabetic patients
* No familial hypercholesterolemia
* No abuse of drugs
* Not more than 4 alcoholic consumption per day with a maximum of 21 per week
* Stable body weight (weight gain or loss \< 3 kg in the past three months)
* No use of medication known to treat blood pressure, lipid or glucose metabolism
* No use of an investigational product within another biomedical intervention trial within the previous 1-month
* No severe medical conditions that might interfere with the study, such as epilepsy, asthma, kidney failure or renal insufficiency, chronic obstructive pulmonary disease, inflammatory bowel diseases, auto inflammatory diseases and rheumatoid arthritis
* No active cardiovascular disease like congestive heart failure or cardiovascular event, such as an acute myocardial infarction or cerebrovascular accident
* Willingness to give up being a blood donor from 8 weeks before the start of the study, during the study and for 4 weeks after completion of the study
* No difficult venipuncture as evidenced during the screening visit
* Willing to comply to study protocol during study
* Informed consent signed

Exclusion Criteria:

* Allergy or intolerance to almonds
* Serum total cholesterol ≥ 8.0 mmol/L
* Serum triacylglycerol ≥ 4.52 mmol/L
* Current smoker, or smoking cessation \<12 months
* Diabetic patients
* Familial hypercholesterolemia
* Abuse of drugs
* More than 4 alcoholic consumptions per day or 21 per week
* Unstable body weight (weight gain or loss \> 3 kg in the past three months)
* Use medication known to treat blood pressure, lipid or glucose metabolism
* Use of an investigational product within another biomedical intervention trial within the previous 1-month
* Severe medical conditions that might interfere with the study, such as epilepsy, asthma, kidney failure or renal insufficiency, chronic obstructive pulmonary disease, inflammatory bowel diseases, auto inflammatory diseases and rheumatoid arthritis
* Active cardiovascular disease like congestive heart failure or cardiovascular event, such as an acute myocardial infarction or cerebrovascular accident
* Not willing to give up being a blood donor from 8 weeks before the start of the study, during the study or for 4 weeks after completion of the study
* Not or difficult to venipuncture as evidenced during the screening visit
* Use of over-the-counter and prescribed medication or supplements, which may interfere with study measurements to be judged by the principal investigator;
* Use of oral antibiotics in 40 days or less prior to the start of the study;
* Blood donation in the past 3 months before the start of the study
* Not willing to comply to study protocol during study or sign informed consent

Primary outcomes:
measure: Insulin sensitivity
timeFrame: Change from control period (week 22 and week 52)
Secondary outcomes:
measure: Glucose concentrations
timeFrame: Glucose will be measured at week 0, week 5, week 10, week 21, week 22, week 30, week 35, week 40, week 51, week 52
measure: Markers for fasting lipid metabolism
timeFrame: These markers will be measured at week 0, week 5, week 10, week 21, week 22, week 30, week 35, week 40, week 51, week 52
measure: LDL cholesterol concentrations
timeFrame: These markers will be calculated from measurements at week 0, week 5, week 10, week 21, week 22, week 30, week 35, week 40, week 51, week 52
measure: C-reactive protein concentrations
timeFrame: CRP will be measured at week 0, week 5, week 10, week 21, week 22, week 30, week 35, week 40, week 51, week 52
measure: Blood pressure
timeFrame: Blood pressure will be measured at week 0, week 5, week 10, week 21, week 22, week 30, week 35, week 40, week 51, week 52
measure: Body weight
timeFrame: Body weight will be measured at week 0, week 5, week 10, week 21, week 22, week 30, week 35, week 40, week 51, week 52
measure: Body circumferences
timeFrame: Waist and hip circumferences will be measured at week 0, week 5, week 10, week 21, week 22, week 30, week 35, week 40, week 51, week 52
measure: Pulse Wave Analysis
timeFrame: Change from control period (week 21 and week 51)
measure: Pulse Wave Velocity
timeFrame: Change from control period (week 21 and week 51)
measure: Retinal microvascular caliber
timeFrame: Change from control period (week 21 and week 51)
measure: Cognitive performance
timeFrame: Cognition will be tested at week 0, week 10, week 21, week 30, week 40, week 51.
measure: Markers for low-grade systemic inflammation
timeFrame: Change from control period (week 21 and week 51)
measure: Markers for endothelial dysfunction
timeFrame: Change from control period (week 21 and week 51)
measure: Markers for postprandial lipid metabolism
timeFrame: Change from control period (week 21 and week 51)
measure: Markers for fasting and postprandial glucose and insulin metabolism
timeFrame: Change from control period (week 21 and week 51)
measure: Markers for liver function
timeFrame: Change from control period (week 21 and week 51)
measure: Markers for nerve growth
timeFrame: Change from control period (week 21 and week 51)
measure: Markers for advanced glycation endproducts
timeFrame: Change from control period (week 21 and week 51)
measure: Nitric oxides concentrations
timeFrame: Change from control period (week 21 and week 51)
measure: Cerebral blood flow
timeFrame: Change from control period (week 22 and week 52)
measure: Fat distribution in abdomen
timeFrame: Change from control period (week 22 and week 52)
measure: Biopsies adipose tissue
timeFrame: Change from control period (week 22 and week 52)
measure: Biopsies muscle tissue
timeFrame: Change from control period (week 22 and week 52)
measure: Lipid oxidation
timeFrame: Indirect calorimetry will be performed at week 21, week 22, week 51, week 52 at several time slots.
measure: Glucose oxidation
timeFrame: Indirect calorimetry will be performed at week 21, week 22, week 51, week 52 at several time slots.
measure: Blood pressure profiles
timeFrame: Change from control period (week 21 and week 51)
measure: Glucose profiles
timeFrame: Change from control period (week 21 and week 51)
measure: Physical activity profiles
timeFrame: Change from control period (week 21 and week 51)
measure: Microbiota composition
timeFrame: Change from control period (week 21 and week 51)
measure: General well-being
timeFrame: General well-being will be tested at week 0, week 10, week 21, week 30, week 40, week 51.
measure: Food frequency
timeFrame: Food frequency will be tested at week 0, week 10, week 21, week 30, week 40, week 51.
measure: Skinfold measurements
timeFrame: Change from control period (week 22 and week 52)
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University, Department of Nutrition and Movement Sciences
state: Limburg
Study officials:
affiliation: Maastricht University
name: Jogchum Plat, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Maastricht University
name: Ronald P Mensink, PhD
role: PRINCIPAL_INVESTIGATOR
References: