Evaluation of the Effects of a Nutritional Intervention of Ketogenic Medium-chain Triglycerides and B-vitamins on Cognitive Functioning in Older Adults With Mild Cognitive Impairment (COGNIKET-MCI)

August 11, 2025 updated by: Société des Produits Nestlé (SPN)

COGNIKET-MCI Trial: A Prospective, Randomized, Double-blind, Placebo-controlled, Multi-center, Multi-country, Pivotal Trial to Study the Effects of a Nutritional Intervention of Ketogenic Medium-chain Triglycerides (kMCT) and B-vitamins on Cognitive Functioning in Older Adults With Mild Cognitive Impairment

Evaluation of the Effects of a Nutritional Intervention of Ketogenic Medium-chain Triglycerides and B-vitamins on Cognitive Functioning in Older Adults With Mild Cognitive Impairment (COGNIKET-MCI)

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

380

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Bron, France
        • Recruiting
        • Hôpital Pierre Wertheimer
        • Contact:
          • Helene Mollion, MD
      • Montpellier, France
        • Recruiting
        • CHU de Montpellier - Hôpital Gui de Chauliac
        • Contact:
          • Karim BENNYS, MD
      • Nantes, France
        • Recruiting
        • CHU de Nantes - Hopital Nord Laennec
        • Contact:
          • Claire Boutoleau-Bretonniere, MD
      • Toulouse, France
        • Recruiting
        • CHU de Toulouse - Gerontopole
        • Contact:
          • Pierre Jean Ousset, MD
  • Germany
      • Bayreuth, Germany
        • Recruiting
        • Klinikum Bayreuth GmbH - Klinik Hohe Warte
        • Contact:
          • Patrick Oschmann, MD
      • Böblingen, Germany
        • Recruiting
        • Studienzentrum für Neurologie und Psychiatrie
        • Contact:
          • Felix Bischof, MD
      • Erbach, Germany
        • Recruiting
        • Neuro Centrum Science GmbH
        • Contact:
          • Gerd Reifschneider, MD
      • Ulm, Germany
        • Recruiting
        • Universitaetsmedizin Ulm
        • Contact:
          • Doerte Polivka, MD
  • Italy
      • Cefalu, Italy
        • Recruiting
        • Foundation Institute G.Giglio
        • Contact:
          • Luigi Grimaldi, MD
      • Genova, Italy
        • Recruiting
        • IRCCS Ospedale Policlinico San Martino
        • Contact:
          • Matteo Pardini, MD
      • Palermo, Italy
        • Recruiting
        • Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone"
        • Contact:
          • Mario Barbagallo, MD
      • Roma, Italy
        • Recruiting
        • Policlinico Universitario Agostino Gemelli
        • Contact:
          • Camillo Marra, MD
      • Roma, Italy
        • Recruiting
        • Azienda Ospedaliera SantAndrea
        • Contact:
          • Franco Giubilei, MD
      • Roma, Italy
        • Recruiting
        • Laboratory of Neuropsyichiatry, Fondazione Santa Lucia IRCCS
        • Contact:
          • Clelia Pellicano, MD
      • Roma, Italy
        • Recruiting
        • AOU Policlinico Umberto I - Sapienza Università di Roma
        • Contact:
          • Giuseppe Bruno, MD
      • Tricase, Italy
        • Recruiting
        • AO Card. G. Panico
        • Contact:
          • Giancarlo Logroscino, MD
  • Spain
      • Alicante, Spain
        • Recruiting
        • Hospital Universitario del Vinalopó
        • Contact:
          • Ana López García, MD
      • Barcelona, Spain
        • Recruiting
        • Fundació ACE
        • Contact:
          • Merce Boada Rovira, MD
      • Madrid, Spain
        • Recruiting
        • HGU Gregorio Marañon
        • Contact:
          • Javier Olazarán, MD
      • Salamanca, Spain
        • Recruiting
        • Unidad de Investigación Neurociencias Centro de Salud San Juan
        • Contact:
          • Angel Luis Montejo Gonzalez, MD
      • Sant Cugat Del Vallès, Spain
        • Recruiting
        • Hospital Universitari General de Catalunya
        • Contact:
          • Ernest Balaguer Martinez, MD
      • Sevilla, Spain
        • Recruiting
        • Hospital Universitario Victoria Eugenia
        • Contact:
          • Felix Vinuela Fernandez, MD
      • Valencia, Spain
        • Recruiting
        • Hospital Universitari i Politècnic La Fe
        • Contact:
          • Miguel Baquero, MD
  • Switzerland
      • Basel, Switzerland, 4055
        • Not yet recruiting
        • Universitäre Altersmedizin Felix Platter
        • Contact:
      • Biel, Switzerland
        • Recruiting
        • Spitalzentrum Centre Hospitalier Biel-Bienne AG (SZB)
        • Contact:
          • Hans-Albert Pihan, MD
      • Lausanne, Switzerland
        • Recruiting
        • CHUV
        • Contact:
          • Olivier Rouaud, MD
  • United Kingdom
      • Crowborough, United Kingdom
        • Recruiting
        • Sussex Partnership NHS Foundation Trust
        • Contact:
          • Naji Tabet, MD
      • Southampton, United Kingdom
        • Recruiting
        • Hampshire & Isle of Wight Healthcare NHS Foundation Trust
        • Contact:
          • Brady McFarlane, MD
  • United States
    • Florida
      • Miami, Florida, United States, 33137
        • Not yet recruiting
        • Stein Gerontological Institute Inc
        • Contact:
    • New York
      • Rochester, New York, United States, 14620

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Have read, understood, and signed the informed consent form (ICF).
  2. Be aged ≥60 years at the time of screening.
  3. Presence of acquired memory complaints with a duration of >3 months. Here we refer to memory/cognitive complaints in a broader sense that can involve other cognitive domains other than memory. (As reported by the participant or reliable trial informant. Trial informants can be a relative, spouse or domestic partner, or close friend who interacts closely enough with the participant to be able to respond to assessments/questionnaires as needed.)

  4. Have a clinical diagnosis of MCI (with a clinical phenotype compatible with AD, insidious SVD [ie, no post-stroke cognitive impairment], or mixed AD/SVD) according to the participating site, or referring center, aligned with international/national standards for MCI diagnosis, and additionally informed by a minimum of one of the following objective criteria as assessed by components of the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery (CERAD NB):

    1. Word list memory task: ≤19,
    2. Word list recall: ≤5,
    3. Fifteen-item subset of the Boston Naming Test (BNT): ≤13,
    4. Constructional praxis recall: ≤7, or
    5. Total CERAD score: ≤70.

  5. Full autonomy for daily living based on the Instrumental Activities of Daily Living (IADL)-Lawton scale:

    1. Score for women: 8 or
    2. Score for men: 5.
  6. Participants must have an available trial informant willing and able to attend the following 3 clinic visits with the participant: V1/randomization, V3/12-month visit, and V4/18-month visit.
  7. Participants must have a trial informant who in the opinion of the investigator, has contact with the trial participant for a sufficient number of hours per week (at least 2 hours per day and a minimum of 4 times per week).
  8. Participants and their trial informants have an adequate ability to read and write, as well as adequate vision and hearing for neuropsychological testing according to the investigator's judgment (corrective aids are allowed).
  9. CDR global score of 0 to 0.5 at screening.
  10. Sexually active females of childbearing potential (defined in further detail in Appendix 1 of the protocol) must practice 2 different highly effective methods of contraception with their heterosexual partner or remain abstinent during the trial and for 30 days after the last dose of nutritional formulation. If employing contraception, the highly effective methods of contraception detailed in Appendix 1 of the protocol must be followed.
  11. Females of childbearing potential must have a negative highly sensitive urine pregnancy test before randomization; a positive urine pregnancy test result must immediately be confirmed using a serum test.
  12. Participants able to satisfactorily comply with the protocol requirements.
  13. Participants willing and able to discontinue all prohibited concomitant medications to meet any protocol-required washout periods before and during the trial period (Section 9.6.1 of the protocol provides more details).

Exclusion Criteria:

  1. Diagnosis of a major neurocognitive disorder according to the 5th Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), or dementia according to the DSM-IV and the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association criteria at the time of enrollment.
  2. MCI related to past or recent concussion, COVID-19, or other specific etiologies (including neurodegenerative disease like Parkinson's disease, multiple sclerosis, Huntington's disease, Lewy-body disease, fronto temporal dementia), or associated with medication/substance use, per the investigator's judgment.
  3. A history of COVID-19 ≤120 days before screening or completion of a vaccination course against severe acute respiratory syndrome coronavirus 2 ≤14 days before screening. The vaccine received must have been authorized for emergency use or approved by the US Food and Drug Administration.
  4. Newly introduced, or change in dose, within the last 2 months before randomization, of physician-prescribed interventions or medications affecting cognition or AD (eg, acetylcholinesterase inhibitors, memantine, anti-amyloid-beta agents), or planned introduction of such medications during the trial.
  5. Participants who will likely require prohibited concomitant therapy during the trial based on the investigator's judgment.
  6. Known history of or ongoing alcohol or substance use disorder, based on medical history, that in the opinion of the investigator may conflict with the participant's participation.
  7. Participants who, in the opinion of the investigator, medical monitor, or sponsor should not participate in the trial.

  8. Symptoms suggestive of depression or anxiety according to the Hospital Anxiety and Depression Scale (HADS):

    1. HADS-D ≥8 or
    2. HADS-A ≥8.
  9. Known active HIV infection, COVID, hepatitis B, or hepatitis C based on medical history.
  10. Participants with epilepsy or a history of seizures, except for a single childhood febrile seizure, post-traumatic seizure, or alcohol withdrawal seizure.
  11. Participants considered to be in poor general health based on the investigator's judgment. Examples include participants who have recent clinically significant weight loss, chronic dehydration or hypovolemia, poor fluid or nutritional intake, or a recent clinically significant infection, as per the investigator's judgment.
  12. Cancer diagnosis in the past 2 years excluding select skin conditions considered to be fully treated (basal cell or squamous cell carcinomas of the skin) or early-stage cancer with excellent prognosis (eg, some prostate cancer conditions) according to the investigator's judgment.
  13. Renal disease (estimated glomerular filtration rate <30 ml/min/1.73m2) based on the investigator's assessment and historical data.
  14. Uncontrolled hypertension (systolic blood pressure >160 mm Hg, and/or diastolic blood pressure >100 mm Hg).
  15. Significant and uncontrolled thyroid disease according to the investigator's judgment.
  16. Any surgery or procedure requiring general anesthesia ≥3 hours, planned, or in the previous 3 months.
  17. Poorly regulated type 2 diabetes (HbA1c >9.0%), or type 2 diabetes that is currently treated with insulin, glucagon-like peptide-1 receptor analog (GLP-1 RA), or a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, or type 1 diabetes.
  18. Vitamin B12 deficiency per the investigator's judgment, or current use of B-vitamin supplementation >200% daily recommended value according to national standards.
  19. Very high or severe hypertriglyceridemia (≥886 mg/dL or 10.0 mmol/L).
  20. Participants who are unable to comply with protocol procedures in the opinion of the investigator (if an individual develops a major neurocognitive disorder during the course of the trial, the appropriateness for the individual to continue will be based on the investigator's judgment).
  21. Have a personal or hierarchical link with the research team members.
  22. Participant who is a shift worker that involves night shifts.
  23. Ongoing/planned pregnancy or breastfeeding at screening (female participants who have a positive pregnancy test result before receiving nutritional formulation will be excluded).
  24. Participants who follow a ketogenic diet or other diet that is intended to influence ketone levels (eg, prolonged fasting, intermittent fasting, ketogenic meal replacement product regimens), or take ketone-, kMCT-, or coconut oil supplementation, or adhere to a diet that excludes milk product use (eg, vegan diet).
  25. Cow's milk protein allergy or intolerance, or other allergy or intolerance to any of the ingredients of the nutritional formulation (eg, medium chain acyl-CoA deficiency, or other fatty acid oxidation disorders).

US protocol specificities:

4. Have MCI (with a clinical phenotype compatible with AD, insidious SVD [ie, no post-stroke cognitive impairment], or mixed AD/SVD) according to the participating site or referring center, as aligned with the National Institute on Aging and the Alzheimer's Association or Mayo Clinic standards for MCI, and additionally informed by a minimum of one of the following objective criteria as assessed by components of the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery (CERADNB):

  1. Word list memory task: ≤19,
  2. Word list recall: ≤5,
  3. Fifteen-item subset of the Boston Naming Test (BNT): ≤13,
  4. Constructional praxis recall: ≤7, or

  5. Total CERAD score: ≤70.

    6. Participants must have an available trial informant willing to attend the following 4 clinic visits with the participant: screening, V1/randomization, V3/12-month visit, and V4/18-month visit.

    9. CDR global score of 0 at screening.

    10. Sexually active females of childbearing potential must practice highly effective methods of contraception with their heterosexual partner (defined in further detail in Appendix 1 of the protocol) or remain abstinent during the trial and for 30 days after the last dose of nutritional formulation. If employing contraception, the highly effective methods of contraception detailed in Appendix 1 of the protocol must be followed.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: BrainXpert
15 g kMCT + B-vitamins (B3, B6, B9/folic acid, and B12) will be provided in powder format
Dietary supplement: BrainXpert
sachet/stickpack of 25 g, has no preservatives, no flavors, no sweeteners, and no colorants.
Placebo Comparator: Placebo

high-oleic acid sunflower oil as a calorie-equivalent, non-ketogenic vegetable oil, non added vitamin product will be provided in a powder format

.
Other: Placebo
high-oleic acid sunflower oil as a calorie-equivalent, non-ketogenic vegetable oil, non added vitamin product will also be provided in a powder format in a sachet/stickpack of 25 g.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Preclinical Alzheimer's Cognitive Composite (PACC) score
Time Frame: 12 months

The change from baseline on the PACC composite cognitive score of episodic memory, timed executive function, and global cognition

PACC has 4 components:

  • Free and Cued Selective Reminding Test (0 (worst)-96 (best recall);
  • Logical Memory Ib (Immediate Recall) from the WMS-IV (Range 0 (worst)-25 (best recall);
  • Wechsler Adult Intelligence scale - revised: Digit Symbol Substitution Test (DSST): (ranges 0 [none]-93 [best performance])
  • Mini Mental State Examination (Range 0 [worst] - 30 [best performance]).

Component scores are transformed using an established normalization method into z-scores. Each of 4 component change scores is divided by baseline sample standard deviation (SD) of that component. These z scores are summed to form the composite score. A z-score of 0 is equal to the mean and implies how many SD higher or lower score as compared with baseline score, with increase signifying improvement.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Preclinical Alzheimer's Cognitive Composite (PACC) (components effects)
Time Frame: 12 months

Individual interventional effects on change from baseline in the individual components of the PACC test (cognitive domains of executive function, episodic memory, and global cognitive function)

PACC has 4 components:

  • Free and Cued Selective Reminding Test (0 (worst)-96 (best recall);
  • Logical Memory Ib (Immediate Recall) from the WMS-IV (Range 0 (worst)-25 (best recall);
  • Wechsler Adult Intelligence scale - revised: Digit Symbol Substitution Test (DSST): (ranges 0 [none]-93 [best performance])
  • Mini Mental State Examination (Range 0 [worst] - 30 [best performance]).
12 months
Montreal Cognitive Assessment (MoCA) score
Time Frame: 12 months
The change from baseline in the Montreal Cognitive Assessment (MoCA) total score Scale range 0 to 30 - higher score indicates better performance
12 months
Preclinical Alzheimer's Cognitive Composite (PACC) accelerated decline
Time Frame: 12 months

Percentage of participants achieving accelerated cognitive decline, defined as a change from baseline in the PACC z-score of at least 1 SD below the mean

PACC has 4 components:

  • Free and Cued Selective Reminding Test (0 (worst)-96 (best recall);
  • Logical Memory Ib (Immediate Recall) from the WMS-IV (Range 0 (worst)-25 (best recall);
  • Wechsler Adult Intelligence scale - revised: Digit Symbol Substitution Test (DSST): (ranges 0 [none]-93 [best performance])
  • Mini Mental State Examination (Range 0 [worst] - 30 [best performance]).

Component scores are transformed using an established normalization method into z-scores. Each of 4 component change scores is divided by baseline sample standard deviation (SD) of that component. These z scores are summed to form the composite score. A z-score of 0 is equal to the mean and implies how many SD higher or lower score as compared with baseline score, with increase signifying improvement.
12 months
Wechsler Memory Scale - Fourth Edition (WMS-IV) Logical Memory IIb Delayed Recall Score accelerated decline
Time Frame: 12 months

Percentage of participants achieving accelerated memory decline, defined as a change from baseline in episodic memory (>3 points) as assessed by the "WMS-IV Logical Memory IIb Delayed Recall Score"

Wechsler Adult Intelligence scale: Digit Symbol Substitution Test (DSST): (ranges 0 [none]-91 [best performance])
12 months
Mini-Mental State Examination (MMSE) score accelerated decline
Time Frame: 12 months
Percentage of participants achieving accelerated cognitive decline, defined as a change from baseline in the Mini-Mental State Examination (MMSE) total score of <24 or a decline of >3 points Scale range 0 to 30 - higher score indicates better performance
12 months
Emergent Adverse Events (Safety and tolerability)
Time Frame: 12 months
Adverse events (AEs), including gastrointestinal tolerability and nausea, vital signs, changes in blood biomarkers (hematology, liver, kidney) over the course of the trial
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Société des Produits Nestlé (SPN)

Collaborators

Syneos Health

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 24, 2024

Primary Completion (Estimated)

December 15, 2027

Study Completion (Estimated)

December 15, 2027

Study Registration Dates

First Submitted

March 28, 2024

First Submitted That Met QC Criteria

March 28, 2024

First Posted (Actual)

April 4, 2024

Study Record Updates

Last Update Posted (Actual)

August 14, 2025

Last Update Submitted That Met QC Criteria

August 11, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2302.CLI

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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