Macronutrient Effects on Alzheimer's Disease (MEAL-2) (MEAL-2)

Macronutrient Effects on Alzheimer's Disease: HTN and IR (Hypertension and Insulin Resistance) (MEAL-2)

This study compares the effects of a one-month diet high in saturated fat (SF), glycemic index (GI), and salt (Na+) to a diet low in these nutritional parameters on memory and other cognitive functions, on MRI measures of brain structure, function, and perfusion, as well as on blood and cerebrospinal fluid levels of amyloid-beta (Aβ), insulin, lipids (total cholesterol, HDL, LDL, oxidized LDL, and triglycerides), cytokines, apolipoprotein E (ApoE), apolipoprotein J, cortisol, soluble low density lipoprotein receptor-related protein (sLRP), and glucose in middle-aged adults (45-65 years of age) with normal cognition or mild cognitive impairment.

Study Overview

• Status: Completed
• Conditions: Insulin Resistance; Prehypertension; Prediabetic State; Mild Cognitive Impairment; Middle Age
• Intervention / Treatment: Other: Low Diet; Other: High Diet

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 41 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects will be middle-aged (45 to 65 years of age) and will fall on the continuum from healthy (no pre-hypertension or insulin resistance) to pre-hypertensive and insulin resistant (pHAIR).
2. Subjects will not be recruited based on memory status but will have normal memory or memory impairment with a diagnosis of mild cognitive impairment (MCI). Those subjects with MCI will have been assessed by physician and neuropsychologist experts and diagnosed with MCI according to Petersen criteria.

Exclusion Criteria:

1. Diabetes not controlled by diet or exercise; current or previous use of diabetes medications
2. Average systolic blood pressure on three occasions <90 or >139 mm/Hg, diastolic blood pressure <60, or current use of anti-hypertensive medications;
3. Clinically significant elevations in liver function tests as follows: SGOT > 1.5 X ULN, SGPT > 1.5 X ULN, Alkaline Phosphate > 1.5 ULN.
4. Clinically significant elevations in lipid profile as follows: LDL>190, triglycerides>340, or total cholesterol>260 and LDL/HDL ratio >3.0.
5. Significant neurologic disease that might affect cognition, including AD (MCI will be allowed), stroke, Parkinson's disease, multiple sclerosis, or severe head injury with loss of consciousness > 30 minutes or with permanent neurologic sequelae;
6. Significant medical illness or organ failure, such as uncontrolled hypertension or cardiovascular disease, chronic obstructive pulmonary disease, liver disease, or kidney disease;
7. Current use of antipsychotic, anti-depressant, anti-convulsant, anticoagulant, anxiolytic, or sedative medications;
8. Current use of cognition-enhancing medications;
9. Current use of glucocorticoids;

10. Current use of cholesterol-lowering medications, including:

    1. HMG-CoA Reductase Inhibitors [Statins: Atorvastatin (Lipitor), Fluvastatin (Lescol or Lescol EX), Lovastatin, Pravastatin (Pravachol), Rosuvastatin (Crestor), Simvastatin (Zocor)]
    2. Bile Acid Resins [Cholestyramine (Questran), Colestipol, Colesevelam (Welchol)]
    3. Fibric Acids Derivatives [Fenofibrate (Tricor), Gemfibrozil]
    4. Combinations [Amlodipine/Atorvastatin, Niacin/Lovastatin (Advicor), Ezetimibe/Simvastatin (Vytorin)]
    5. Miscellaneous Categories [Ezetimibe (Zetia), Niacin aka Nicotinic acid (Niaspan)
    6. Over-the-counter [Red yeast rice, Niacinamide, Omega 3 fatty acids (fish or flax seed), Slo-Niacin]
11. Common allergies/sensitivities to the following food products: dairy, wheat, gluten, tree nuts or peanuts, eggs, corn, seafood and soy. Other food sensitivities will be assessed on a case-by-case basis.
12. BMI ≤ 18.5
13. Current weight <110 pounds
14. Clinically significant iron deficiency: Hemoglobin <13.5 for white males, <12.2 for white females, <12.5 for black males, and <11.5 for black females.
15. If female, menstruation in the past 12 months or hysterectomy and current hormone replacement therapy medication.
16. Major digestive disorders, absorption issues, or surgeries, including bowel resection, inflammatory bowel diseases (Ulcerative colitis or Crohn's disease), or irritable bowel syndrome (IBS) with a tendency toward diarrhea

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low Diet; Diet intervention consisting of foods with low saturated fats, low glycemic index and low salt	Other: Low Diet; a 28-day course of 3 meals per day plus 2 snack that are either low in saturated fats, glycemic index and salt.
Experimental: High Diet; Diet intervention consisting of foods with high saturated fats, high glycemic index and high salt	Other: High Diet; a 28-day course of 3 meals per day plus 2 snack that are either high in saturated fats, glycemic index and salt.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cerebrospinal fluid levels of Alzheimer's disease biomarkers (CSF beta-amyloid 42)	CSF beta-amyloid 42	After 4 week diet intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in brain structure	MRI entorhinal cortex and white matter volume	After 4 week diet intervention
Changes in adipose tissue distribution (Change in dual energy x-ray absorptiometry (DEXA) scan and CT measures of central and subcutaneous body fat)	Change in DEXA and CT measures of central and subcutaneous body fat	After 4 week diet intervention
Changes in cognition (Change in delayed memory and executive function composites)	Change in delayed memory and executive function composites	After 4 week diet intervention
Change in brain function as measured by MRI	Change in resting state default mode network connectivity	After 4 week diet intervention
Change in brain perfusion	Change in cerebral perfusion	After 4 week diet intervention

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: December 19, 2014
• First Submitted That Met QC Criteria: June 2, 2015
• First Posted (Estimate): June 4, 2015

Study Record Updates

• Last Update Posted (Actual): August 9, 2018
• Last Update Submitted That Met QC Criteria: August 7, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Endocrine System Diseases; Diabetes Mellitus; Neurodegenerative Diseases; Hyperinsulinism; Dementia; Tauopathies; Cognition Disorders; Prehypertension; Prediabetic State; Alzheimer Disease; Cognitive Dysfunction; Insulin Resistance
• Other Study ID Numbers: IRB 00022512

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No