TABLE 5.
RCTs in the pipeline, investigating the use of ketogenic diet/agents on patients with Alzheimer disease or mild cognitive impairment1
| Clinical trial identifier | Study | Collaborators | Design | Intervention/comparator duration | Intervention | Comparator | Estimated study duration | Primary outcomes | Secondary outcomes |
|---|---|---|---|---|---|---|---|---|---|
| NCT03860792 | TDAD2 | 1) University of Kansas Medical Center2) NIA | Parallel, single-blind (outcomes assessor) RCT | 3 mo | KD (1:1) (70% fat, <10% CHO, and 20% protein) | TLC diet (20%–35% fat, 50%–60% CHO, and ∼15% protein as energy. Fat intake is comprised of <7% SFA, ≤20% MUFA, and ≤10% PUFA as total energy. Consumption of ≤200 cholesterol mg/d, ≥2 servings of fruit and ≥5 servings of vegetables daily). | October 2019 to November 2023 | 1) ADAS-Cog2) MMSE3) Logical memory test (WMS-R)4) Stroop5) CDR | 1) Cerebral NAA concentration2) Blood platelet mitochondrial function3) Self-reported symptoms4) Blood ketone concentrations5) Days positive for urinary ketones6) Dietary intake |
| NCT02912936 | MINT-012 | 1) University of British Columbia2) Université de Sherbrooke | Parallel RCT with quadruple masking | 10 d | Ketogenic MCT drink (lactose-free skim milk drink containing 25 g MCT oil per 250 mL). | Placebo drink (lactose-free skim milk drink containing high-oleic sunflower oil with the equivalent amount of energy as the active arm). | September 2016 to December 2019 | 1) Adverse events2) Plasma ketone concentrations in ascending MCT dose | 1) AUC of MCT2) Δ in cerebral metabolic rate of glucose, blood flow, and MRS after a ketogenic drink3) Physical activity |
| NCT03472664 | BEAT-AD3 | 1) Wake Forest University2) NIA | Parallel, double-blind RCT | 4 mo | Modified Mediterranean KD (low-CHO/high-fat diet) including extra virgin olive oil, fish, lean meats, <20 g CHO/d, and a daily MV tablet. | AHA diet (low fat/high CHO). Diet includes fat intake <40 g/d, fruits, vegetables, CHO, adequate fiber, and a daily MV tablet. | July 2018 to April 2023 | 1) CSF Aβ42 | 1) CSF Aβ42/tau2) PACC3) Cerebral blood flow with ASL |
| NCT02709356 | MCT-MA4 | 1) Université de Sherbrooke2) Fondation Vitae | Parallel,5 single-blind (patients) RCT | 1 mo | Supplementation of caprylic acid MCT oil [60% capric acid (10:0) + 40% caprylic acid] per day. | Supplementation of 30 g MCT oil (100% caprylic acid) per day. | October 2015 to February 2018 | 1) Brain glucose uptake2) Brain AcAc uptake | NR |
AcAc, acetoacetate; ADAS-Cog, Alzheimer's Disease Assessment Scale-Cognitive subscale (58); AHA, American Heart Association; ASL, arterial spin labeling; Aβ42, Amyloid β 42; BEAT-AD, Brain Energy for Amyloid Transformation in Alzheimer's Disease; CDR, Clinical Dementia Rating (70); CHO, carbohydrates; CSF, cerebrospinal fluid; KD, ketogenic diet; MCT, medium-chain triglyceride; MCT-MA, Medium Chain Triglycerides and brain Metabolism in Alzheimer's disease; MINT-01, Medium Chain Triglyceride INTervention for patients with Alzheimer disease; MMSE, Mini-Mental State Exam (59); MRS, magnetic resonance spectroscopy; MV, multivitamin; NAA, N-acetylaspartate; NIA, National Institute on Aging; NR, not reported; PACC, Preclinical Alzheimer Cognitive Composite (Free and Cued Selective Reminding Test, Logical Memory IIa, Digit Symbol Substitution Test, MMSE); RCT, randomized controlled trial; TDAD, Therapeutic Diets in Alzheimer's Disease; TLC, Therapeutic Lifestyle Changes (131); WMS-R, Wechsler Memory Scale-Revised (78).
RCTs not yet recruiting.
RCTs with a “recruiting” status on www.clinicaltrials.gov.
“Completed” RCT status.
Registration indicates parallel design; however, the explanation of the procedures denotes a crossover intervention.