Clinical trial NCT02463084: Macronutrient Effects on Alzheimer's Disease (MEAL-2)
Official title: Macronutrient Effects on Alzheimer's Disease: HTN and IR (Hypertension and Insulin Resistance) (MEAL-2)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Prediabetic State
Insulin Resistance
Middle Age
Prehypertension
Mild Cognitive Impairment
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
First posted: 2015-06-04
Enrollment: 60
Sex: ALL
Minimum age (years): 45
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in cerebrospinal fluid levels of Alzheimer's disease biomarkers (CSF beta-amyloid 42)
timeFrame: After 4 week diet intervention
Secondary outcomes:
measure: Changes in brain structure
timeFrame: After 4 week diet intervention
measure: Changes in adipose tissue distribution (Change in dual energy x-ray absorptiometry (DEXA) scan and CT measures of central and subcutaneous body fat)
timeFrame: After 4 week diet intervention
measure: Changes in cognition (Change in delayed memory and executive function composites)
timeFrame: After 4 week diet intervention
measure: Change in brain function as measured by MRI
timeFrame: After 4 week diet intervention
measure: Change in brain perfusion
timeFrame: After 4 week diet intervention
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Suzanne Craft, PhD
role: PRINCIPAL_INVESTIGATOR
References: