Macronutrient Effects on Alzheimer's Disease (MEAL-2) (MEAL-2)
Primary Purpose
Prediabetic State, Insulin Resistance, Middle Age
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Low Diet
High Diet
Sponsored by
About this trial
This is an interventional prevention trial for Prediabetic State
Eligibility Criteria
Inclusion Criteria:
- 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).
- 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:
- Diabetes not controlled by diet or exercise; current or previous use of diabetes medications
- Average systolic blood pressure on three occasions <90 or >139 mm/Hg, diastolic blood pressure <60, or current use of anti-hypertensive medications;
- Clinically significant elevations in liver function tests as follows: SGOT > 1.5 X ULN, SGPT > 1.5 X ULN, Alkaline Phosphate > 1.5 ULN.
- Clinically significant elevations in lipid profile as follows: LDL>190, triglycerides>340, or total cholesterol>260 and LDL/HDL ratio >3.0.
- 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;
- Significant medical illness or organ failure, such as uncontrolled hypertension or cardiovascular disease, chronic obstructive pulmonary disease, liver disease, or kidney disease;
- Current use of antipsychotic, anti-depressant, anti-convulsant, anticoagulant, anxiolytic, or sedative medications;
- Current use of cognition-enhancing medications;
- Current use of glucocorticoids;
Current use of cholesterol-lowering medications, including:
- HMG-CoA Reductase Inhibitors [Statins: Atorvastatin (Lipitor), Fluvastatin (Lescol or Lescol EX), Lovastatin, Pravastatin (Pravachol), Rosuvastatin (Crestor), Simvastatin (Zocor)]
- Bile Acid Resins [Cholestyramine (Questran), Colestipol, Colesevelam (Welchol)]
- Fibric Acids Derivatives [Fenofibrate (Tricor), Gemfibrozil]
- Combinations [Amlodipine/Atorvastatin, Niacin/Lovastatin (Advicor), Ezetimibe/Simvastatin (Vytorin)]
- Miscellaneous Categories [Ezetimibe (Zetia), Niacin aka Nicotinic acid (Niaspan)
- Over-the-counter [Red yeast rice, Niacinamide, Omega 3 fatty acids (fish or flax seed), Slo-Niacin]
- 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.
- BMI ≤ 18.5
- Current weight <110 pounds
- 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.
- If female, menstruation in the past 12 months or hysterectomy and current hormone replacement therapy medication.
- 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
Sites / Locations
- Wake Forest Baptist Health
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Low Diet
High Diet
Arm Description
Diet intervention consisting of foods with low saturated fats, low glycemic index and low salt
Diet intervention consisting of foods with high saturated fats, high glycemic index and high salt
Outcomes
Primary Outcome Measures
Change in cerebrospinal fluid levels of Alzheimer's disease biomarkers (CSF beta-amyloid 42)
CSF beta-amyloid 42
Secondary Outcome Measures
Changes in brain structure
MRI entorhinal cortex and white matter volume
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
Changes in cognition (Change in delayed memory and executive function composites)
Change in delayed memory and executive function composites
Change in brain function as measured by MRI
Change in resting state default mode network connectivity
Change in brain perfusion
Change in cerebral perfusion
Full Information
NCT ID
NCT02463084
First Posted
December 19, 2014
Last Updated
August 7, 2018
Sponsor
Wake Forest University Health Sciences
1. Study Identification
Unique Protocol Identification Number
NCT02463084
Brief Title
Macronutrient Effects on Alzheimer's Disease (MEAL-2)
Acronym
MEAL-2
Official Title
Macronutrient Effects on Alzheimer's Disease: HTN and IR (Hypertension and Insulin Resistance) (MEAL-2)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
March 2013 (undefined)
Primary Completion Date
June 2016 (Actual)
Study Completion Date
June 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Wake Forest University Health Sciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prediabetic State, Insulin Resistance, Middle Age, Prehypertension, Mild Cognitive Impairment
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Low Diet
Arm Type
Experimental
Arm Description
Diet intervention consisting of foods with low saturated fats, low glycemic index and low salt
Arm Title
High Diet
Arm Type
Experimental
Arm Description
Diet intervention consisting of foods with high saturated fats, high glycemic index and high salt
Intervention Type
Other
Intervention Name(s)
Low Diet
Intervention Description
a 28-day course of 3 meals per day plus 2 snack that are either low in saturated fats, glycemic index and salt.
Intervention Type
Other
Intervention Name(s)
High Diet
Intervention Description
a 28-day course of 3 meals per day plus 2 snack that are either high in saturated fats, glycemic index and salt.
Primary Outcome Measure Information:
Title
Change in cerebrospinal fluid levels of Alzheimer's disease biomarkers (CSF beta-amyloid 42)
Description
CSF beta-amyloid 42
Time Frame
After 4 week diet intervention
Secondary Outcome Measure Information:
Title
Changes in brain structure
Description
MRI entorhinal cortex and white matter volume
Time Frame
After 4 week diet intervention
Title
Changes in adipose tissue distribution (Change in dual energy x-ray absorptiometry (DEXA) scan and CT measures of central and subcutaneous body fat)
Description
Change in DEXA and CT measures of central and subcutaneous body fat
Time Frame
After 4 week diet intervention
Title
Changes in cognition (Change in delayed memory and executive function composites)
Description
Change in delayed memory and executive function composites
Time Frame
After 4 week diet intervention
Title
Change in brain function as measured by MRI
Description
Change in resting state default mode network connectivity
Time Frame
After 4 week diet intervention
Title
Change in brain perfusion
Description
Change in cerebral perfusion
Time Frame
After 4 week diet intervention
10. Eligibility
Sex
All
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
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).
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:
Diabetes not controlled by diet or exercise; current or previous use of diabetes medications
Average systolic blood pressure on three occasions <90 or >139 mm/Hg, diastolic blood pressure <60, or current use of anti-hypertensive medications;
Clinically significant elevations in liver function tests as follows: SGOT > 1.5 X ULN, SGPT > 1.5 X ULN, Alkaline Phosphate > 1.5 ULN.
Clinically significant elevations in lipid profile as follows: LDL>190, triglycerides>340, or total cholesterol>260 and LDL/HDL ratio >3.0.
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;
Significant medical illness or organ failure, such as uncontrolled hypertension or cardiovascular disease, chronic obstructive pulmonary disease, liver disease, or kidney disease;
Current use of antipsychotic, anti-depressant, anti-convulsant, anticoagulant, anxiolytic, or sedative medications;
Current use of cognition-enhancing medications;
Current use of glucocorticoids;
Current use of cholesterol-lowering medications, including:
HMG-CoA Reductase Inhibitors [Statins: Atorvastatin (Lipitor), Fluvastatin (Lescol or Lescol EX), Lovastatin, Pravastatin (Pravachol), Rosuvastatin (Crestor), Simvastatin (Zocor)]
Bile Acid Resins [Cholestyramine (Questran), Colestipol, Colesevelam (Welchol)]
Fibric Acids Derivatives [Fenofibrate (Tricor), Gemfibrozil]
Combinations [Amlodipine/Atorvastatin, Niacin/Lovastatin (Advicor), Ezetimibe/Simvastatin (Vytorin)]
Miscellaneous Categories [Ezetimibe (Zetia), Niacin aka Nicotinic acid (Niaspan)
Over-the-counter [Red yeast rice, Niacinamide, Omega 3 fatty acids (fish or flax seed), Slo-Niacin]
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.
BMI ≤ 18.5
Current weight <110 pounds
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.
If female, menstruation in the past 12 months or hysterectomy and current hormone replacement therapy medication.
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Suzanne Craft, PhD
Organizational Affiliation
Wake Forest University Health Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Wake Forest Baptist Health
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Macronutrient Effects on Alzheimer's Disease (MEAL-2)
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