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Feasibility and Efficacy of Dietary Interventions for Older Adults With Subjective Cognitive Decline

Primary Purpose

Alzheimer Disease, Cognitive Impairment

Status
Withdrawn
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
MAD
MIND
Sponsored by
Johns Hopkins University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer Disease

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Self-experienced persistent decline in cognitive capacity compared with a previously normal status that is unrelated to an acute event and that is not explained by a psychiatric disorder or neurological disease apart from Alzheimer's disease, medical disorder, medication, or substance use, with the onset of decline no longer than 5 years prior to study participation
  • Clinical Dementia Rating (CDR) score equal to 0
  • Montreal Cognitive Assessment (MoCA) equal to or greater than 26
  • Age 60 years or older
  • Personal physician clearance
  • Willing to comply with all requirements of the study protocol and provide informed consent

Exclusion Criteria:

  • Diagnosis of mild cognitive impairment (MCI), Alzheimer's disease (AD), or other dementia
  • Current psychiatric diagnosis
  • Unstable metabolic condition (documented on screening laboratory studies performed within the past year)
  • persistent hyponatremia (sodium < 130 mg/dL twice within the past year)
  • severe hypernatremia (sodium > 150 mg/dL twice within the past year)
  • hypoglycemia (glucose < 50 mg/dL)
  • hypocalcemia (albumin-corrected calcium < 8 mg/dL)
  • Type-I diabetes
  • Type-2 diabetes requiring any medication other than metformin. (Please note that patients with type-2 diabetes may require medication adjustment if on the very low-carb modified Atkins diet.)
  • Liver failure
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or ammonia > 5x upper limits of normal
  • hyperbilirubinemia
  • total bilirubin > 15 mg/dL
  • direct bilirubin > 5 mg/dL
  • Hypercholesterolemia (on medication, if needed)
  • fasting total cholesterol > 300 mg/dL
  • fasting LDL cholesterol > 200 mg/dL
  • Known fatty acid oxidation disorder or pyruvate carboxylase deficiency
  • Body mass index < 18.5
  • History of ischemic or hemorrhagic stroke
  • History of nephrolithiasis
  • History of myocardial infarction or known coronary artery disease
  • Acute pancreatitis
  • Multiple food allergies or strict dietary requirements
  • Any other concerns about nutritional status (e.g., recent unexplained weight loss, difficulty swallowing)

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Modified Atkins Diet (MAD)

    MIND diet

    Arm Description

    A diet that can produce ketones

    Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND). A diet that has been indicated to be helpful in preventing or decreasing cognitive decline.

    Outcomes

    Primary Outcome Measures

    Change in Memory Functioning Questionnaire (MFQ)
    This is a self-report assessment of cognitive decline. It is rated on a 1-7 scale, with 1 indicating "major problems" and 7 indicating "no problems." It includes 8 sections, each including 1-18 sub-questions. It will be assessed by comparing changes in scores between groups and across time (12 weeks).
    Change in Loewenstein-Acevedo Scales of Semantic Interference and Learning (LASSI-L)
    This is an assessment of verbal learning and memory for lists of 15 words. More words learned and remembered indicate better learning and memory. It will be assessed by comparing changes in scores between groups and across time (12 weeks).
    Change in Para-Rodriguez Short-term Visual Memory Binding Test (SVMBT)
    This is an assessment of visual recognition memory for shapes and colors. More accurate recognition indicates better recognition memory. It will be assessed by comparing changes in scores between groups and across time (12 weeks).
    Change in Ketone levels
    This is detected in urine and measured in mg/dL, with higher levels indicating greater production of ketones and greater adherence to the MAD diet. Adherence will be assessed by percent of participants in the MAD group in at least moderate ketosis (>40 mg/dl) at 3 or more follow-up visits.
    MIND Diet Score
    This is assessed by dietitian review of participants daily food logs. Scores range from 0 (not at all adherent) to 15 (perfectly adherent). Any score greater than 9 is considered adherent. It will be assessed by percent of participants in the MIND group with scores of at least 9 at 3 or more follow-up visits.
    ApoE epsilon 4 status
    This is a genetic marker of Alzheimer's disease risk. It will be coded as positive (one or more epsilon 4 alleles) or negative (no epsilon 4 alleles). It will be evaluated by stratifying the sample by the presence of at least one ε4 allele and conditioning the efficacy analyses by this variable.

    Secondary Outcome Measures

    Change in Trail Making Test
    This is a timed test of processing speed and executive functioning. Faster time to completion and fewer errors indicate better processing speed and executive functioning. It will be assessed by comparing changes in scores between groups and across time (12 weeks).
    Change in Prospective Memory Test
    This is a test of remembering to ask that a borrowed item be returned. The possible scores range from 0 (no cues needed to remember to ask) to 4 (4 cues needed to remember to ask). More cues required indicates worse prospective memory. It will be assessed by comparing changes in scores between groups and across time (12 weeks).
    Change in Geriatric Anxiety Scale
    This is a self-report measure of symptoms of anxiety in older persons. It is rated on a 0 (not at all) to 3 (all of the time) scale. Scores range from 0-90, with higher scores indicating more anxiety. It will be assessed by comparing changes in scores between groups and across time (12 weeks).
    Change in Geriatric Depression Scale
    This is a self-report measure of symptoms of depression in older persons. Items are rated as yes/no. Scores range from 0-30, with higher scores indicating more depression. It will be assessed by comparing changes in scores between groups and across time (12 weeks).

    Full Information

    First Posted
    June 21, 2018
    Last Updated
    October 1, 2019
    Sponsor
    Johns Hopkins University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03585907
    Brief Title
    Feasibility and Efficacy of Dietary Interventions for Older Adults With Subjective Cognitive Decline
    Official Title
    Feasibility and Efficacy of Dietary Interventions for Older Adults With Subjective Cognitive Decline
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2019
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Lack of funding
    Study Start Date
    September 2, 2019 (Anticipated)
    Primary Completion Date
    September 1, 2021 (Anticipated)
    Study Completion Date
    September 1, 2021 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Johns Hopkins University

    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 aims to assess if/how dietary interventions (i.e., the Modified Atkins Diet (MAD) and/or the Mediterranean-Dietary Approaches to Stop Hypertension (DASH) Intervention for Neurodegenerative Delay (MIND)) might prevent, delay onset, alleviate symptoms, or otherwise alter the course of subjective cognitive decline (SCD) likely due to Alzheimer's disease (AD). We hypothesize that participants will tolerate both diets well and that the MAD will result in more favorable changes in cognition and other functioning.
    Detailed Description
    Specific aims are to 1) to establish the feasibility of implementing the MAD in older adults with subjective cognitive decline (SCD) likely due to AD, 2) to examine whether changes in participants' cognition, mood, or other functioning are more favorable in patients using the MAD than in patients using the MIND diet, 3) to assess the role of Apolipoprotein E (ApoE) epsilon 4 genotype in response to the MAD in individuals with SCD. We hypothesize that 1) participants will be able to adhere to and tolerate the MAD and the MIND, determined by review of patients' food records and urine ketone production, 2) participants who adhere to the MAD will demonstrate a more favorable change on neuropsychological tests than participants on the MIND diet, and 4) the neuropsychological effects of the MAD will be greatest in those participants without a ε4 allele of the ApoE gene.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Alzheimer Disease, Cognitive Impairment

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Masking
    Outcomes Assessor
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Modified Atkins Diet (MAD)
    Arm Type
    Experimental
    Arm Description
    A diet that can produce ketones
    Arm Title
    MIND diet
    Arm Type
    Active Comparator
    Arm Description
    Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND). A diet that has been indicated to be helpful in preventing or decreasing cognitive decline.
    Intervention Type
    Dietary Supplement
    Intervention Name(s)
    MAD
    Intervention Description
    A high fat, low carbohydrate diet
    Intervention Type
    Dietary Supplement
    Intervention Name(s)
    MIND
    Intervention Description
    A combination of the Mediterranean and DASH diets
    Primary Outcome Measure Information:
    Title
    Change in Memory Functioning Questionnaire (MFQ)
    Description
    This is a self-report assessment of cognitive decline. It is rated on a 1-7 scale, with 1 indicating "major problems" and 7 indicating "no problems." It includes 8 sections, each including 1-18 sub-questions. It will be assessed by comparing changes in scores between groups and across time (12 weeks).
    Time Frame
    Baseline/week-0, week-6, completion/week-12
    Title
    Change in Loewenstein-Acevedo Scales of Semantic Interference and Learning (LASSI-L)
    Description
    This is an assessment of verbal learning and memory for lists of 15 words. More words learned and remembered indicate better learning and memory. It will be assessed by comparing changes in scores between groups and across time (12 weeks).
    Time Frame
    Baseline/week-0, week-6, completion/week-12
    Title
    Change in Para-Rodriguez Short-term Visual Memory Binding Test (SVMBT)
    Description
    This is an assessment of visual recognition memory for shapes and colors. More accurate recognition indicates better recognition memory. It will be assessed by comparing changes in scores between groups and across time (12 weeks).
    Time Frame
    Baseline/week-0, week-6, completion/week-12
    Title
    Change in Ketone levels
    Description
    This is detected in urine and measured in mg/dL, with higher levels indicating greater production of ketones and greater adherence to the MAD diet. Adherence will be assessed by percent of participants in the MAD group in at least moderate ketosis (>40 mg/dl) at 3 or more follow-up visits.
    Time Frame
    Checked by the participant daily, for 12 weeks/3 months (i.e., from the start day of the diet until the end of the 12 weeks) and checked by the study staff at each study visit (i.e., baseline/week-0, week-3, week-6, and completion/week-12)
    Title
    MIND Diet Score
    Description
    This is assessed by dietitian review of participants daily food logs. Scores range from 0 (not at all adherent) to 15 (perfectly adherent). Any score greater than 9 is considered adherent. It will be assessed by percent of participants in the MIND group with scores of at least 9 at 3 or more follow-up visits.
    Time Frame
    12 weeks/3 months (i.e., from the start day of the diet until the end of the 12 weeks)
    Title
    ApoE epsilon 4 status
    Description
    This is a genetic marker of Alzheimer's disease risk. It will be coded as positive (one or more epsilon 4 alleles) or negative (no epsilon 4 alleles). It will be evaluated by stratifying the sample by the presence of at least one ε4 allele and conditioning the efficacy analyses by this variable.
    Time Frame
    Tested via venipuncture or buccal swab at baseline/week-0
    Secondary Outcome Measure Information:
    Title
    Change in Trail Making Test
    Description
    This is a timed test of processing speed and executive functioning. Faster time to completion and fewer errors indicate better processing speed and executive functioning. It will be assessed by comparing changes in scores between groups and across time (12 weeks).
    Time Frame
    Baseline, week-6, week-12
    Title
    Change in Prospective Memory Test
    Description
    This is a test of remembering to ask that a borrowed item be returned. The possible scores range from 0 (no cues needed to remember to ask) to 4 (4 cues needed to remember to ask). More cues required indicates worse prospective memory. It will be assessed by comparing changes in scores between groups and across time (12 weeks).
    Time Frame
    Baseline, week-6, week-12
    Title
    Change in Geriatric Anxiety Scale
    Description
    This is a self-report measure of symptoms of anxiety in older persons. It is rated on a 0 (not at all) to 3 (all of the time) scale. Scores range from 0-90, with higher scores indicating more anxiety. It will be assessed by comparing changes in scores between groups and across time (12 weeks).
    Time Frame
    Baseline, week-6, week-12
    Title
    Change in Geriatric Depression Scale
    Description
    This is a self-report measure of symptoms of depression in older persons. Items are rated as yes/no. Scores range from 0-30, with higher scores indicating more depression. It will be assessed by comparing changes in scores between groups and across time (12 weeks).
    Time Frame
    Baseline, week-6, week-12
    Other Pre-specified Outcome Measures:
    Title
    Change in Cognitive decline concern questionnaire
    Description
    This is a one question questionnaire that asks how concerned/worried a person is about their subjective cognitive decline on a 1 (majorly worried) to 7 (not at all worried) scale, with higher scores indicating a greater degree of concern/worry. It will be assessed by comparing changes in scores between groups and across time (12 weeks).
    Time Frame
    Baseline, week-6, week-12

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    60 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Self-experienced persistent decline in cognitive capacity compared with a previously normal status that is unrelated to an acute event and that is not explained by a psychiatric disorder or neurological disease apart from Alzheimer's disease, medical disorder, medication, or substance use, with the onset of decline no longer than 5 years prior to study participation Clinical Dementia Rating (CDR) score equal to 0 Montreal Cognitive Assessment (MoCA) equal to or greater than 26 Age 60 years or older Personal physician clearance Willing to comply with all requirements of the study protocol and provide informed consent Exclusion Criteria: Diagnosis of mild cognitive impairment (MCI), Alzheimer's disease (AD), or other dementia Current psychiatric diagnosis Unstable metabolic condition (documented on screening laboratory studies performed within the past year) persistent hyponatremia (sodium < 130 mg/dL twice within the past year) severe hypernatremia (sodium > 150 mg/dL twice within the past year) hypoglycemia (glucose < 50 mg/dL) hypocalcemia (albumin-corrected calcium < 8 mg/dL) Type-I diabetes Type-2 diabetes requiring any medication other than metformin. (Please note that patients with type-2 diabetes may require medication adjustment if on the very low-carb modified Atkins diet.) Liver failure Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or ammonia > 5x upper limits of normal hyperbilirubinemia total bilirubin > 15 mg/dL direct bilirubin > 5 mg/dL Hypercholesterolemia (on medication, if needed) fasting total cholesterol > 300 mg/dL fasting LDL cholesterol > 200 mg/dL Known fatty acid oxidation disorder or pyruvate carboxylase deficiency Body mass index < 18.5 History of ischemic or hemorrhagic stroke History of nephrolithiasis History of myocardial infarction or known coronary artery disease Acute pancreatitis Multiple food allergies or strict dietary requirements Any other concerns about nutritional status (e.g., recent unexplained weight loss, difficulty swallowing)

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided

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