This study aims to determine whether a keto-like supplement relative to placebo results in functional brain changes during fMRI tasks evaluating positive and negative valence in individuals with moderate to severe depression. In this double-blind randomized placebo-controlled trial, 75 individuals with a Patient Health Questionnaire (PHQ-9) scale score ≥ 10 (MDD) will be enrolled to participate in an 8-week treatment study to obtain 60 completers. Participants will be randomized with a 1-1 ratio to receive the keto-like supplement (n= 30 completers) or placebo (n=30 completers) taken orally three times per day for 8 weeks. Participants will undergo a 10.5-hour screening/baseline evaluation visit split over 2 days at week 0 including questionnaires, neuroimaging before and after supplement or placebo administration and blood draws, office visits at week 2 (1.5 hours), week 4 (3 hours), week 6 (0.5 hours), week 8 (6 hours), a follow-up visit at week 10 (1.5 hours) and two phone calls between visits (weeks 1 and 3) during which a brief clinical assessment will be obtained (10 minutes each). The total time involved in the study is approximately 23.5 hours.
Meets the Diagnostic and statistical manual - 5 (DSM-5) diagnostic criteria for MDD without psychotic features (past or present), as confirmed by the M.I.N.I v7.0
PHQ-9 score of ≥10
C-Reactive Protein (CRP) value > 1
Age 18-65
Has a current or recent history of clinically significant suicidality
Has a history of moderate or severe substance or alcohol use disorder according to DSM-5 criteria, except nicotine or caffeine, within 12 months before screening
Has positive test result(s) for alcohol or drugs of abuse (including methadone, opiates, cocaine, cannabinoids, amphetamine/methamphetamine and ecstasy)
Has a current diagnosis of a psychotic disorder (e.g. schizophrenia, bipolar disorder), an eating disorder (e.g. anorexia, bulimia), or learning disability or a personality disorder that is considered by the investigator to interfere with the ability of the subject to adhere to the protocol (e.g. narcissistic personality, borderline personality disorder)