TABLE 1.
Study design and protocol characteristics of the included RCTs investigating the effects of ketogenic therapy on patients with mild cognitive impairment/Alzheimer disease1
| First author | Brandt (45) | Craft (46) | Fortier (47) | Henderson (48) | Henderson (49) | Krikorian (50) | Ota (51)2 | Rebello (52) | Reger (53) | Torosyan (54) |
|---|---|---|---|---|---|---|---|---|---|---|
| Study name | — | BEAM | BENEFIC | — | — | — | — | — | — | — |
| Study duration | October 2015 to April 2018 | February 2015 to April 2017 | 2015 until now | October 2004 to June 2006 | October 2004 to June 2006 | NR | October 2012 to August 2013 | NR | NR | |
| Publication year | 2019 | 2016 | 2019 | 2009 | 2011 | 2012 | 2019 | 2015 | 2004 | 2018 |
| Publication type | Full-text | Abstract | Full-text | Full-text | Full-text | Full-text | Full-text | Commentary | Brief communication | Full-text |
| Journal | J Alzheimers Dis | Alzheimers Dement | Alzheimers Dement | Nutr Metab | BMC Med Genet | Neurobiol Aging | Neurosci Lett | BBA Clin | Neurobiol Aging | Exp Gerontol |
| Origin | USA | USA | Canada | USA | USA | USA | Japan | USA | USA | USA |
| Registry | NCT02521818 | NCT02984540 | NCT02551419 | NCT00142805 | NCT00142805 | NCT00777010 | NR | NCT01669200 | NR | NR |
| Funding | 1) William & Ella Owens Medical Research Fndn2) Bright Focus Fndn3) NCATS4) Hass Avocado Board | 1) Wake Forest Baptist Medical Center2) NIA3) Hartman Family Fndn4) Dept of Defense5) NCATS | 1) Part-the-Cloud, AA, USA2) Mitacs3) Université de Sher-brooke | Accera, Inc. | Accera, Inc. | 1) Robert C & Veronica Atkins Fndn2) NIA3) Indiana AD Center | 1) Food Science Institute Fndn, Japan2) Meiji Co. Ltd. | NR | NR | 1) John Douglas French AD Fndn 2) Accera, Inc. |
| Ethical permission | Johns Hopkins University, USA | Wake Forest School of Medicine, USA | CIUSSS de l'Estrie–CHUS, Sherbrooke, Quebec, Canada | Essex Institutional Review Board, Lebanon, NJ, USA | Essex Institutional Review Board, Lebanon, NJ, USA | University of Cincinnati, USA | National Center of Neurology & Psychiatry, Japan | Pennington Biomedical Research Center, USA | NR | NR |
| RCT design | Parallel | Crossover | Parallel | Parallel | Parallel | Parallel | Crossover | Parallel | Crossover | Parallel |
| Randomization | Random number table | NR | Randomization sequence with 6 consecutive blocks of 10 participants (1:1 ratio) | Permutated block randomization code with a block size of 4 (1:1 ratio) | NR | NR | Randomized sequence NOD | Random number table NOD | NR | By the pharmacy, NOD |
| Masking | Single-blind | Single-blind (outcomes assessor) | Quadruple-blind | Double-blind | Double-blind | Open label | Double-blind | Double-blind | Double-blind | Double-blind |
| Multicenter | No | No | No | ✓ (23 centers) | ✓ (23 centers) | No | No | No | No | No |
| Concerns | No flowchart, discrepancies between PP analysis and reported dropouts | More outcomes were reported in the protocol registry, lack of flowchart, no tables | Lack of flowchart, most data presented in figures | Patients at each stage were not reported, no flowchart, lack of RCT protocol registry | Very low sample power, lack of statistical analyses and flowchart | Lack of flowchart, data presented in figures | Uneven sample allocation, no flowchart, low sample power in controls | |||
| Oxford quality score (44) | 2 | −1 | 2 | 3 | 3 | −1 | 0 | 1 | 0 | 2 |
AA, Alzheimer's Association; AD, Alzheimer Disease; BEAM, Brain Energy and Memory; BENEFIC, Brain ENErgy Fitness, Imaging and Cognition; CIUSSS de l'Estrie–CHUS: Centre Intégré Universitaire de Santé et de Services Sociaux de l'Estrie–Centre Hospitalier Universitaire de Sherbrooke; Dept, Department; Fndn, Foundation; NCATS, National Center for Advancing Translational Sciences; NIA, National Institute of Aging; NOD, not other defined; NR, not reported; PP, per protocol; RCT, randomized controlled trial.
The study had a double design: an RCT (presented in the table) and a long-term clinical trial without a comparator (omitted for not fulfilling the inclusion criteria).