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

Mild Cognitive Impairment Clinical Trial

— MEAL-2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02463084
• Other study ID #: IRB 00022512
• Status: Completed
• Phase: N/A
• Start date: March 2013
• Est. completion date: June 2016

Study information

• Verified date: August 2018
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: June 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 45 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Cognitive Dysfunction
• Insulin Resistance
• Middle Age
• Mild Cognitive Impairment
• Prediabetic State
• Prehypertension

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in cerebrospinal fluid levels of Alzheimer's disease biomarkers (CSF beta-amyloid 42)	CSF beta-amyloid 42	After 4 week diet intervention
Secondary	Changes in brain structure	MRI entorhinal cortex and white matter volume	After 4 week diet intervention
Secondary	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
Secondary	Changes in cognition (Change in delayed memory and executive function composites)	Change in delayed memory and executive function composites	After 4 week diet intervention
Secondary	Change in brain function as measured by MRI	Change in resting state default mode network connectivity	After 4 week diet intervention
Secondary	Change in brain perfusion	Change in cerebral perfusion	After 4 week diet intervention