Clinical trial NCT06347315: 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)
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Mild Cognitive Impairment
Lead sponsor: Société des Produits Nestlé (SPN)
Sponsor class: INDUSTRY
First posted: 2024-04-04
Enrollment: 380
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: parallel and pivotal
Primary purpose: OTHER

Brief summary: 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)


Eligibility criteria: 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).

Primary outcomes:
measure: Preclinical Alzheimer's Cognitive Composite (PACC) score
timeFrame: 12 months
Secondary outcomes:
measure: Preclinical Alzheimer's Cognitive Composite (PACC) (components effects)
timeFrame: 12 months
measure: Montreal Cognitive Assessment (MoCA) score
timeFrame: 12 months
measure: Preclinical Alzheimer's Cognitive Composite (PACC) accelerated decline
timeFrame: 12 months
measure: Wechsler Memory Scale - Fourth Edition (WMS-IV) Logical Memory IIb Delayed Recall Score accelerated decline
timeFrame: 12 months
measure: Mini-Mental State Examination (MMSE) score accelerated decline
timeFrame: 12 months
measure: Emergent Adverse Events (Safety and tolerability)
timeFrame: 12 months
Other outcomes:
Locations:
city: Bron
country: France
facility: Hôpital Pierre Wertheimer
city: Montpellier
country: France
facility: CHU de Montpellier - Hôpital Gui de Chauliac
city: Nantes
country: France
facility: CHU de Nantes - Hôpital Nord Laennec
city: Toulouse
country: France
facility: CHU de Toulouse - Gerontopole
city: Bayreuth
country: Germany
facility: Klinikum Bayreuth GmbH - Klinik Hohe Warte
city: Böblingen
country: Germany
facility: Studienzentrum für Neurologie und Psychiatrie
city: Erbach
country: Germany
facility: Neuro Centrum Science GmbH
city: Ulm
country: Germany
facility: Universitaetsmedizin Ulm
city: Cefalu
country: Italy
facility: Foundation Institute G.Giglio
city: Genova
country: Italy
facility: IRCCS Ospedale Policlinico San Martino
city: Palermo
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone"
city: Roma
country: Italy
facility: AOU Policlinico Umberto I - Sapienza Università di Roma
city: Roma
country: Italy
facility: Azienda Ospedaliera SantAndrea
city: Roma
country: Italy
facility: Laboratory of Neuropsyichiatry, Fondazione Santa Lucia IRCCS
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli
city: Tricase
country: Italy
facility: AO Card. G. Panico
city: Alicante
country: Spain
facility: Hospital Universitario del Vinalopó
city: Barcelona
country: Spain
facility: Fundaciò ACE
city: Madrid
country: Spain
facility: HGU Gregorio Marañón
city: Salamanca
country: Spain
facility: Unidad de Investigación Neurociencias Centro de Salud San Juan
city: Sant Cugat Del Vallès
country: Spain
facility: Hospital Universitari General de Catalunya
city: Sevilla
country: Spain
facility: Hospital Universitario Victoria Eugenia
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Basel
country: Switzerland
facility: Universitare Altersmedizin FELIX PLATTER
city: Biel
country: Switzerland
facility: Spitalzentrum Centre Hospitalier Biel-Bienne AG (SZB)
city: Lausanne
country: Switzerland
facility: CHUV
city: Crowborough
country: United Kingdom
facility: Sussex Partnership NHS foundation Trust
city: Southampton
country: United Kingdom
facility: Hampshire & Isle of Wight Healthcare NHS Foundation Trust
Study officials:
References: