Brain Energy for Amyloid Transformation in Alzheimer's Disease Study (BEAT-AD)
Hjerneenergi til amyloid transformation i AD (BEAT-AD) undersøgelse
Brain Energy for Amyloid Transformation in AD (Alzheimers sygdom) eller BEAT-AD-studiet vil sammenligne virkningerne af en ketogen diæt med lavt kulhydratindhold og en fedtfattig diæt hos voksne med mild kognitiv svækkelse. De indsamlede data vil hjælpe med at bestemme, om diætinterventioner inducerer ændringer i kognitiv funktion, cerebral blodgennemstrømning og niveauer af visse proteiner og hormoner i kropsvæsker.
Undersøgelsen vil omfatte frivillige, som har mild kognitiv svækkelse, som vil blive tilfældigt tildelt til at modtage enten en ketogen diæt med lavt kulhydratindhold eller en fedtfattig diæt i 16 uger, med opfølgende vurdering 8 uger efter diætens afslutning. Undersøgelsesforanstaltninger, klinikbesøg og telefonsessioner vil finde sted ved baseline og gennem hele den 24-ugers undersøgelse.
Gruppe 2 vil omfatte frivillige med let kognitiv svækkelse. Denne gruppe vil gennemføre en 16-ugers fedtfattig diætundersøgelse med opfølgende vurdering 8 uger efter diætens endelige afslutning. Undersøgelsesforanstaltninger, klinikbesøg og telefonsessioner vil finde sted i løbet af den 24-ugers undersøgelse.
Deltageren vil følge enten en diæt med lavt kulhydrat eller fedtfattigt, som vil blive individuelt planlagt med hjælp fra en diætist. Efter at have gennemført undersøgelsesdiæten i 16 uger, vil deltagerne genoptage deres normale kost. De sidste besøg finder sted i uge 24 (8 uger efter afslutningen af diæten). Ved afslutningen af det 24-ugers studie vil deltagerne få mulighed for at mødes med undersøgelsens diætist for uddannelse og hjælp til planlægning af en sund kost.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
Denne undersøgelse vil undersøge virkningerne af en 4-måneders modificeret middelhavs-ketogen diæt sammenlignet med en American Heart Association-diæt (AHAD - et regime, der har vist sig at reducere risikoen for hjerte-kar-sygdomme). Vi vil undersøge kosteffekter på AD-biomarkører, på kognition og på neuroimaging målinger af blodgennemstrømning. Vores undersøgelse vil udvide tidligere resultater på flere vigtige måder ved: 1) at bruge en modificeret middelhavs-ketogen diæt i stedet for en traditionel ketogen diæt, som har potentialet for større langsigtet compliance og sundhedsmæssige fordele; 2) at øge prøvestørrelsen og varigheden af diætinterventionen; 3) at undersøge potentielle mekanismer for kosteffekter, der kan resultere i nye biomarkører og terapeutiske mål; og 4) at undersøge vigtige behandlingsresponsvariabler såsom Apolipoprotein E (ApoE) genotype, amyloid positivitet og metabolisk status, der kunne informere præcise medicintilgange til diætordination.
Voksne med amnestisk mild kognitiv svækkelse (MCI) vil blive randomiseret på et 1:1-skema for at modtage enten en 4-måneders Modificeret Mediterranean-Ketogenic Diet (MMKD) eller American Heart Association Diet (AHAD) intervention. Diætinterventioner vil være ækvikaloriske med deltagernes normale diæter. Personlig ernæringsvejledning og menuer vil blive leveret, og overholdelse vil blive vurderet af en registreret diætist. Den primære investigator vil være ansvarlig for den overordnede overvågning af undersøgelsesdeltagernes data og sikkerhed med bistand fra medlemmer af undersøgelsespersonalet og Data and Safety Monitoring Board (DSMB), som vil være ansvarlig for at overvåge forskningsdeltagernes sikkerhed .
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Ikke anvendelig
Kontakter og lokationer
Studiesteder
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North Carolina
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Winston-Salem, North Carolina, Forenede Stater, 27157
- Wake Forest Baptist Medical Center
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Beskrivelse
Inklusionskriterier:
- Diagnose af amnestisk mild kognitiv svækkelse
- En informant (studiepartner) i stand til at give sikkerhedsoplysninger om deltageren
- Stabil medicinsk tilstand (generelt 3 måneder før screeningsbesøg) efter undersøgelseslægens skøn
- Stabil på medicin (generelt 4 uger før screeningsbesøget) efter undersøgelseslægens skøn
- Kunne gennemføre baseline vurderinger
Ekskluderingskriterier:
- Diagnose af neurodegenerativ sygdom (undtagen MCI);
- Anamnese med et klinisk signifikant slagtilfælde
- Aktuelle beviser eller historie i det seneste år med fokal hjernelæsion, hovedskade med tab af bevidsthed eller DSM-IV-kriterier for enhver større psykiatrisk lidelse, herunder psykose, svær depression, bipolar lidelse, alkohol- eller stofmisbrug
- Sensorisk svækkelse (dvs.: visuel eller auditiv), der ville forhindre deltageren i at deltage i protokollen
- Diabetes, der kræver aktuel brug af diabetesmedicin
- Klinisk signifikante stigninger i leverfunktionstests
- Aktiv neoplastisk sygdom (stabil prostatacancer og ikke-melanom hudkræft er tilladt)
- Anamnese med epilepsi eller anfald inden for det seneste år
- Kontraindikationer for MR (klaustrofobi, kraniofaciale metalimplantater, pacemakere)
- Betydelig medicinsk sygdom eller organsvigt, såsom ukontrolleret hypertension eller kardiovaskulær sygdom, kronisk obstruktiv lungesygdom, leversygdom eller nyresygdom
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Dobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Eksperimentel: Modificeret middelhavsketogen diæt
MMKD er en diæt med lavt kulhydrat/fedtindhold, der sigter mod at inducere ketose, som den eksperimentelle diæt i den foreslåede undersøgelse. Deltagere på MMKD vil holde deres daglige kulhydratforbrug under 20 gram om dagen i løbet af den 4 måneder lange intervention. MMKD-gruppen vil blive forsynet med ekstra jomfru olivenolie under deres personlige besøg for at bruge som en kilde til fedt i deres kost, og vil opfordres til at spise rigeligt med fisk, magert kød og næringsrige fødevarer, der opfylder kravet om <20 gram samlede kulhydrater om dagen. Deltagerne vil modtage et dagligt multivitamin (Centrum Silver) i løbet af undersøgelsen og instrueret i at tage 1 tablet hver dag, mens de er på diæt. |
Modificeret middelhavs-ketogen diæt er en diæt med lavt kulhydrat/fedtindhold.
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Eksperimentel: American Heart Association diæt
American Heart Association Diet (AHAD), er en diæt med lavt fedtindhold/højt kulhydratindhold (<40 gram/dag), der vil blive brugt som kontroldiæt.
Deltagere på AHAD vil blive opfordret til at begrænse deres mængde fedtindtag til <40 gram/dag, mens de spiser rigeligt med frugt, grøntsager og kulhydrater, der indeholder tilstrækkelige fibre.
Deltagerne vil modtage det samme daglige multivitamintilskud (Centrum Silver) i løbet af undersøgelsen og instrueret i at tage 1 tablet hver dag, mens de er på diæt.
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American Heart Association Diet er en diæt med lavt fedtindhold/højt kulhydratindhold.
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Cerebrospinal Fluid Abeta42
Tidsramme: baseline
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Aβ42 is a a key Alzheimer's disease biomarker that reflects pathological aggregation of amyloid in the brain.
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baseline
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Cerebrospinal Fluid Abeta42
Tidsramme: week 16
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Aβ42 is a a key Alzheimer's disease biomarker that reflects pathological aggregation of amyloid in the brain.
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week 16
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Cerebrospinal Fluid Aβ40
Tidsramme: baseline, week 16
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Aβ40 is a peptide biomarker primarily used in the evaluation and diagnosis of Alzheimer's disease and other neurodegenerative conditions
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baseline, week 16
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Cerebrospinal Fluid Total Tau
Tidsramme: baseline, week 16
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total tau is a general indicator of neuronal degeneration and injury
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baseline, week 16
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Cerebrospinal Fluid ptau181
Tidsramme: baseline, week 16
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ptau181 (phosphorylated tau 181) biomarker is a specialized protein used as a primary diagnostic indicator for Alzheimer's disease
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baseline, week 16
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Cerebrospinal Fluid NfL
Tidsramme: baseline, week 16
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NfL (Neurofilament Light Chain) biomarker is a tool for diagnosing, monitoring, and predicting the progression of various neurodegenerative and neurological diseases
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baseline, week 16
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Plasma Aβ42
Tidsramme: baseline, week 16
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Aβ42 is a a key Alzheimer's disease biomarker that reflects pathological aggregation of amyloid in the brain.
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baseline, week 16
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Plasma Aβ40
Tidsramme: baseline, week 16
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Aβ40 is a peptide biomarker primarily used in the evaluation and diagnosis of Alzheimer's disease and other neurodegenerative conditions
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baseline, week 16
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Plasma p-tau217
Tidsramme: baseline, week 16
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p-tau217 (phosphorylated tau at threonine 217) is a biomarker used to detect and predict the brain changes associated with Alzheimer's disease
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baseline, week 16
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Plasma Phosphorylated Tau 181
Tidsramme: baseline, week 16
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pTau181 (phosphorylated tau 181) is a biomarker that serves as a primary diagnostic indicator for Alzheimer's disease
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baseline, week 16
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Plasma NfL
Tidsramme: baseline, week 16
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NfL (Neurofilament Light Chain) biomarker is a tool for diagnosing, monitoring, and predicting the progression of various neurodegenerative and neurological diseases
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baseline, week 16
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Hemoglobin A1c
Tidsramme: baseline, week 16
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Hemoglobin A1c measures your average blood sugar levels over the past 2 to 3 months.
Below 5.7% is normal, 5.7-6.4% indicates prediabetes, 6.5% or higher indicates diabetes.
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baseline, week 16
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Triglyceride Level
Tidsramme: baseline, week 16
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The level of triglycerides (a type of fat) in blood with less than 150 mg/dL being normal.
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baseline, week 16
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LDL Level
Tidsramme: baseline, week 16
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LDL (low-density lipoprotein) is the amount of "bad" cholesterol in the blood.
The optimal level is less than 100 mg/dL.
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baseline, week 16
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HDL Level
Tidsramme: baseline, week 16
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HDL (High-Density Lipoprotein) blood test measures the amount of "good" cholesterol in the blood.
Optimal level is ≥ 60 mg/dL.
Low HDL (<40 mg/dL for men, <50 mg/dL for women) indicates a higher risk for cardiovascular disease.
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baseline, week 16
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Total Cholesterol Level
Tidsramme: baseline, week 16
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Measure of overall amount of cholesterol in the blood, which includes both "bad" (LDL) and "good" (HDL) cholesterol.
Desirable level is less than 200 mg/dL with higher levels indicating greater risk for heart attack and stroke.
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baseline, week 16
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Ketones Level
Tidsramme: baseline, week 16
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A blood ketone test specifically measures beta-hydroxybutyrate, the primary ketone in your blood.
Under 0.6 mmol/L normal or negative.
0.6 to 1.5 mmol/L slightly elevated, body is in ketosis (burning fat for fuel).
1.6 to 3.0 mmol/L elevated, risk for diabetic ketoacidosis.
Over 3.0 mmol/L high, indicates potentially dangerous levels that require emergency medical attention.
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baseline, week 16
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Glucose Level
Tidsramme: baseline, week 16
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Level of blood glucose with normal being less than 100 mg/dL while fasting.
Fasting levels of 100 to 125 mg/dL indicate prediabetes.
Fasting levels of 126 mg/dL or higher (on more than one occasion) indicate diabetes.
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baseline, week 16
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MRI Pseudo Continuous Arterial Spin Labeling Hippocampal Uptake
Tidsramme: baseline, week 16
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Cerebral blood flow will be measured with pseudo continuous arterial spin labeling MRI and voxel based analyses will be conducted to determine diet-induced changes and their relationship to cognitive and biomarker outcomes.
Healthy adult gray matter typically ranges between 50 to 70 ml/100g/min.
Lower than typical range indicates reduced cerebral blood flow.
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baseline, week 16
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MRI Pseudo Continuous Arterial Spin Labeling Meta-Region of Interest Uptake
Tidsramme: baseline, week 16
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Pseudo Continuous Arterial Spin Labeling measures regional cerebral blood flow.
Meta-Region of Interest combines data from multiple predefined brain regions into a single composite uptake score.
Higher values in mL/100g/min indicate greater tissue perfusion, while lower values reflect reduced blood flow.
Normal gray matter perfusion in a healthy adult typically ranges between 50 and 60 mL/100g/min, while white matter generally measures around 20 mL/100g/min.
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baseline, week 16
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MRI Neurite Orientation Dispersion and Density Imaging-Neurite Density Index (NODDI-NDI) Hippocampal Uptake
Tidsramme: baseline, week 16
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NODDI-NDI measures the packing and density of neurites (axons and dendrites) in the hippocampal region of the brain.
NDI values drop in the hippocampus as neurites degenerate during Alzheimer's disease or normal aging.
NDI is expressed as a decimal value typically falling between 0 and 1.
A value of 0 represents an area with no neurites (e.g., pure cerebrospinal fluid), while a value closer to 1 indicates a highly dense network of axons or dendrites.
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baseline, week 16
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MRI Neurite Orientation Dispersion and Density Imaging-Neurite Density Index (NODDI-NDI) Meta-Region of Interest Uptake
Tidsramme: baseline, week 16
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NODDI-NDI measures the packing and density of neurites in the region of interest in the brain.
NDI values drop as neurites degenerate during Alzheimer's disease or normal aging.
NDI is expressed as a decimal value typically falling between 0 and 1.
A value of 0 represents an area with no neurites (e.g., pure cerebrospinal fluid), while a value closer to 1 indicates a highly dense network of axons or dendrites.
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baseline, week 16
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MRI Neurite Orientation Dispersion and Density Imaging-Isotropic Volume Fraction (NODDI-ISOVF) Hippocampal Uptake
Tidsramme: baseline, week 16
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ISOVF measures the proportion of water molecules that are diffusing freely and isotropically in the hippocampal region of the brain.
Elevated ISOVF is frequently observed in Alzheimer's disease, cognitive decline, aging, and infection burdens, reflecting a breakdown of tissue structure.
Expressed as a value between 0 and 1 with a higher number indicating a higher level of free, isotropic water.
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baseline, week 16
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MRI Neurite Orientation Dispersion and Density Imaging-Isotropic Volume Fraction (NODDI-ISOVF) Meta-Region of Interest (ROI) Uptake
Tidsramme: baseline, week 16
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ISOVF Meta-ROI measures the proportion of water molecules that are diffusing freely and isotropically within a region of interests in the brain.
Elevated ISOVF is frequently observed in Alzheimer's disease, cognitive decline, aging, and infection burdens, reflecting a breakdown of tissue structure.
Expressed as a value between 0 and 1 with a higher number indicating a higher level of free, isotropic water.
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baseline, week 16
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MRI Neurite Orientation Dispersion and Density Imaging Orientation Dispersion Index (NODDI-ODI) Hippocampal Uptake
Tidsramme: baseline, week 16
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NODDI ODI (Orientation Dispersion Index) is used to quantify the spatial configuration and branching of neurites (axons and dendrites) in hippocampal region of the brain.
It measures how widely the orientations of neurites spread out in space within a voxel.
Low ODI indicates highly aligned or parallel fibers, typical of coherent white matter tracts.
High ODI indicates highly dispersed or fanned-out fibers, typical of gray matter or areas with complex fiber crossings.
ODI ranges from 0 to 1, where values closer to 0 represent fibers pointing in nearly the same direction (low dispersion).
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baseline, week 16
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MRI Neurite Orientation Dispersion and Density Imaging Orientation Dispersion Index (NODDI-ODI) Meta-Region of Interest (ROI) Uptake
Tidsramme: baseline, week 16
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NODDI ODI (Orientation Dispersion Index) is used to quantify the spatial configuration and branching of neurites (axons and dendrites) in the region of interest in the brain.
It measures how widely the orientations of neurites spread out in space within a voxel.
Low ODI indicates highly aligned or parallel fibers, typical of coherent white matter tracts.
High ODI indicates highly dispersed or fanned-out fibers, typical of gray matter or areas with complex fiber crossings.
ODI ranges from 0 to 1, where values closer to 0 represent fibers pointing in nearly the same direction (low dispersion).
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baseline, week 16
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Modified Preclinical Alzheimer Cognitive Composite 5 (mPACC5) Score
Tidsramme: Week 16
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The modified Preclinical Alzheimer Cognitive Composite 5 (mPACC5) measures cognitive changes associated with Alzheimer's-related brain pathology.
It aggregates z-scores from five specific cognitive tests across four domains: episodic memory (delayed recall tests), timed executive function (speed and processing tasks), semantic memory (verbal fluency tests), global cognition (overall mental status exams).
Total Z-score range: healthy /unimpaired baseline -0.50 to +1.00, mild cognitive impairment -2.50 to -0.50, dementia -3.50 to -2.50.
The central value of the mPACC5 is 0.
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Week 16
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Alzheimer's Disease Assessment Scale-Cognitive 12 (ADAS-Cog 12) Score
Tidsramme: baseline, week 16
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The ADAS-Cog 12 is a psychometric instrument that evaluates memory, attention, reasoning, language, orientation, and praxis.
A higher score indicates more impairment.
Scores range from 0-85 with higher scores indicating greater cognitive impairment.
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baseline, week 16
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Neuropsychiatric Inventory Questionnaire (NPI-Q) Score
Tidsramme: baseline, week 16
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The NPI-Q is widely used to assess the presence of mood disorders in geriatric populations.
The NPI-Q measures 12 symptom categories and is scored on a scale of 0-36.
A higher score indicates a higher burden of neuropsychiatric symptoms.
A score of 0 indicates no symptoms are present.
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baseline, week 16
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Geriatric Depression Scale Score
Tidsramme: baseline, week 16
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The Geriatric Depression Scale is a well-validated self-report questionnaire used frequently in clinical and research settings to assess mood in older adults.
Total score range is 0-15 with 0-4 normal range (no risk of depression indicated), 5-8 mild depressive symptoms, 9-11 moderate depressive symptoms, 12-15 severe depressive symptoms.
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baseline, week 16
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Andre resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Pittsburgh Sleep Quality Index
Tidsramme: baseline, week 16
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Pittsburgh Sleep Quality Index was inadvertently listed as a secondary outcome in the protocol but was actually an exploratory outcome.
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baseline, week 16
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Epworth Sleepiness Scale
Tidsramme: baseline, week 16
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Epworth Sleepiness Scale was inadvertently listed as a secondary outcome in the protocol but was actually an exploratory outcome.
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baseline, week 16
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WatchPAT Sleep Stage Time
Tidsramme: baseline, week 16
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WatchPAT sleep stage time was inadvertently listed as a secondary outcome in the protocol but was actually an exploratory outcome
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baseline, week 16
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Samarbejdspartnere og efterforskere
Samarbejdspartnere
Efterforskere
- Ledende efterforsker: Suzanne Craft, PhD, Wake Forest University Health Sciences
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- IRB00049474
- 1R01AG055122-01 (U.S. NIH-bevilling/kontrakt)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
IPD-planbeskrivelse
IPD-delingstidsramme
IPD-delingsadgangskriterier
IPD-deling Understøttende informationstype
- STUDY_PROTOCOL
- SAP
- ICF
- ANALYTIC_CODE
- CSR
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
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