Clinical trial NCT06444568: Modified Ketogenic Diet in Amnestic Mild Cognitive Impairments
Official title: Efficacy of Modified Ketogenic Diet in Amnestic Mild Cognitive Impairments
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Amnestic Mild Cognitive Disorder
Amnestic Mild Cognitive Impairment
Lead sponsor: Saglik Bilimleri Universitesi
Sponsor class: OTHER
Collaborators: name: Ankara University
First posted: 2024-06-05
Enrollment: 36
Sex: ALL
Minimum age (years): 65
Maximum age (years): 80
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This clinical study aims to examine the effectiveness of a 12-week modified ketogenic diet (MKD) intervention, especially on cognitive functions, in individuals diagnosed with amnestic-mild cognitive impairment (aMCI) and to compare the effects of control groups (passive or active).

Accordingly, a sample of 36 older adults aged 65-80 years diagnosed with aMCI will be randomized into 3 different groups: passive control (without any intervention), active control (MIND: Mediterranean-DASH Intervention for Neurodegenerative Delay diet) or intervention (MKD). They will be monitored according to targeted criteria throughout the 12-week study protocol.

The main questions this study aims to answer are:

* Does a 12-week MKD intervention improve cognitive functions in aMCI?
* Does the effectiveness of the 12-week MKD intervention in aMCI (i.e., in terms of cognitive function, physical and functional measures, or metabolic/inflammatory biomarkers) differ from control groups?

Expected from participants during the study protocol:

* Participants assigned to the passive control arm are expected to come to the research center at the beginning (week 0) and end (week 12) of the protocol and participate in evaluations.
* Participants assigned to the active control (MIND diet) or intervention (MKD) arm are expected to adhere to assigned dietary therapy, keep a weekly food diary, and have weekly phone calls or online meetings with the dietitian to follow up on the diet. These participants assigned to the diet groups are expected to come to the research center at weeks 0, 4, 8, and 12 to participate in the evaluations.

Detailed description: This study is an open-label, parallel-group randomized controlled clinical trial. The researchers hypothesized that a 12-week modified ketogenic diet (MKD) intervention in participants diagnosed with amnestic-mild cognitive impairments (aMCI) would improve cognitive functions and progression criteria compared to control groups.

The research sample will consist of individuals diagnosed with aMCI, and 36 volunteers, 12 individuals, were randomly assigned to three different research arms according to the block randomization method. To evaluate this sample size in the "repeated measures ANOVA" test of three independent groups with a medium effect size (f:0.30), 5% significance level (α), and 90% power (1-β) in the power analysis, the sample size should be at least 27 individuals has been calculated.

According to the dropout rate (25%) reported in similar ketogenic diet intervention studies in the literature, 36 was targeted as the sample size of the study.

For confidentiality purposes, the coding method will be used in the processing of data according to the study arms and the order of inclusion in the protocol (i.e., PC-1, AC-1, or KD-1, passive/active control, and the ketogenic diet, respectively). It is planned to evaluate cognitive functions with ADAS-Cog (Alzheimer's Disease Assessment Scale: Cognitive Subscale), physical performance with motor-cognitive dual-task and hand grip strength, and functional capacity with Lawton instrumental activities of daily living scale. Yesavage Geriatric Depression Scale-short form (GDS-15), which will also be used as an eligibility criterion, will be used to evaluate mood.

Intervention: After examining the food consumption diaries (7 days), diet planning will be made for the appropriate study arm (MIND or MKD). The daily energy of the diets is eucaloric in two diet groups, and daily energy will be determined according to the daily average energy intake determined by the nutritional status assessment of the individual and the ESPEN (European Society for Clinical Nutrition and Metabolism) consensus recommendation.

Ketogenic diet calculations will be made through the KetoDietCalculator program. The two basic principles of the planned modified ketogenic diet are 1) protein intake of 1 g/kg per day, and 2) a ketogenic diet ratio 1:1. According to the determined daily energy intake, the contribution of macronutrients to daily energy will be determined by the ketogenic diet ratio. Controlling protein intake per body weight is not a routine practice in ketogenic diet applications, and in this study - to preserve lean body mass as much as possible in elderly individuals - the ESPEN consensus recommendation will be taken into account in the calculations.

The MIND diet, which is the control group diet, will be planned following the 14 dietary guidelines defined elsewhere, and the above criteria will be applied in the same way in determining daily energy. MIND is a diet whose neuroprotective properties are currently accepted, with its ability to delay cognitive function loss and dementia supported by many population-based prospective studies.

Following the dietary training, both groups will be given brochures containing the basic principles and instructions of the diet and educational materials containing recipes developed specifically for the diet group. Compliance with the ketogenic diet is evaluated according to the individuals' serum ketone level (compliance criterion: β-hydroxybutyrate/BHB: 0.5-2.5 mmol/L) and food consumption diaries evaluated at 4, 8, and 12 weeks. Compliance with the MIND diet, which is the active control diet, will be evaluated with the MIND diet score calculated from weekly food consumption diaries (compliance criterion: MIND score \>10/14).

In evaluating all outcome variables, the per-protocol analysis method will be applied to examine only participants who completed the research protocol. The intention-to-treat method will be used to evaluate some secondary outcome variables (i.e., biomarkers and anthropometry). Changes in primary and secondary outcome variables between the intervention and control groups during the study will be evaluated by repeated measures ANOVA test. All statistical tests will be evaluated in the SPSS (Statistical Package for Social Science) program at 90% power and 5% significance level.

Eligibility criteria: Inclusion Criteria:

* Having been diagnosed with "amnestic mild cognitive impairment/disorder (aMCI)" by the clinician after the evaluation of cognitive functions according to the neuropsychological evaluation method (0.5 according to the Clinical Dementia Rating Scale (CDR).)
* Having at least 6 years of education.

Exclusion Criteria:

* Under the age of 65 or over the age of 80.
* Diagnosis of neurological (other than MCI) or psychological diseases.
* GDS-15 score \> 5 (baseline)
* Kidney/pancreas/liver diseases or dysfunctions, Type 1 diabetes (and Type II diabetic patients receiving insulin replacement therapy), cancer, metabolic diseases (fatty acid oxidation defect, etc.), thyroid dysfunction, pulmonary or autoimmune diseases, head trauma, history of any cardiovascular event (i.e., stroke, myocardial infarction) in the last year.
* Hypercholesterolemia (fasting T-C \>300 mg/dL or LDL-C \>200 mg/dL), non-reference B12 or folate levels according to biochemical tests performed in the last year.
* Nutritional risks (chewing/swallowing difficulties, history of involuntary weight loss in the last 6 months, body mass index \< 22 kg/m2).
* Use of internal device/implant (pacemaker or hearing aid, etc.).
* Medication use (individuals using anticholinergic, antidementia, and opioid class drugs will be excluded; individuals using antidepressant class drugs will be included in the study on the condition that it has been continued for at least 3 months and there is no change in drug type and dose during the study protocol.)

Primary outcomes:
measure: ADAS-Cog score
timeFrame: Baseline (week:0) - end of the protocol (week:12)
Secondary outcomes:
measure: Dual-task (Physical performance)
timeFrame: Baseline (week:0) - week:4 - week:8 - end of the protocol (week:12)
measure: Handgrip strength (kg)
timeFrame: Baseline (week:0) - week:4 - week:8 - end of the protocol (week:12)
measure: Total cholesterol (TC, mg/dL)
timeFrame: Baseline (week:0) - end of the protocol (week:12)
measure: Low-density lipoprotein cholesterol (LDL-C, mg/dL)
timeFrame: Baseline (week:0) - end of the protocol (week:12)
measure: High-density lipoprotein cholesterol (HDL-C, mg/dL)
timeFrame: Baseline (week:0) - end of the protocol (week:12)
measure: Tumor Necrosis Factor-alpha (TNF-α, pg/mL)
timeFrame: Baseline (week:0) - end of the protocol (week:12)
measure: β-hydroxybutyrate (β-HB, mmol/L)
timeFrame: Baseline (week:0) - week:4 - week:8 - end of the protocol (week:12)
measure: Serum malondialdehyde (MDA) (nmol/mL)
timeFrame: Baseline (week:0) - end of the protocol (week:12)
measure: Serum Glutathione peroxidase (GSH-Px, U/mL)
timeFrame: Baseline (week:0) - end of the protocol (week:12)
Other outcomes:
measure: Geriatric Depression Scale-short form (GDS-15) score
timeFrame: Baseline (week:0) - end of the protocol (week:12)
measure: Body weight (kg)
timeFrame: Baseline (week:0) - week:4 - week:8 - end of the protocol (week:12)
measure: Body height (cm)
timeFrame: Baseline (week:0)
measure: Body Mass Index (BMI, kg/m^2)
timeFrame: Baseline (week:0) - week:4 - week:8 - end of the protocol (week:12)
measure: Fat-free mass (kg, via body composition analysis)
timeFrame: Baseline (week:0) - week:4 - week:8 - end of the protocol (week:12)
measure: Fat mass (kg, via body composition analysis)
timeFrame: Baseline (week:0) - week:4 - week:8 - end of the protocol (week:12)
measure: Weekly reported side effects relevant ketogenic diet
timeFrame: week 0-12
Locations:
city: Ankara
country: Turkey
facility: Gulhane Faculty of Medicine & Gulhane Training and Research Hospital
Study officials:
affiliation: Saglik Bilimleri University
name: Mehmet I Naharcı, Prof.
role: STUDY_CHAIR
References:
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