Ketogenic Agent Tricaprilin Shows Potential Benefit in Pilot Study of Migraine


At month 2 of a 3-month treatment period, investigators observed an improvement of 2.75 days favoring tricaprilin.

Mark Bloch, associate professor at the University of New South Wales, Sydney

Mark Bloch

Findings from a pilot study (NCT04437199) assessing up to 60 g/day of tricaprilin (Cerecin), an investigational ketogenic compound, suggested potential benefit in treating patients with migraine. At the end of the 3-month treatment period, some patients opted to enter the Compassionate Access Program, which provides continued access to the therapy for up to 1 year after completion of the clinical study.1,2

Otherwise known as the RELIEF study, 81 individuals who entered the study with 4-24 migraine headache days (MHDs) per month were randomly assigned to tricaprilin (n = 40) or placebo (n = 41). Among the 61 individuals (31 per arm) who had available efficacy data, there was no meaningful difference in the primary end point of change in MHDs at month 3; however, investigators did observe a mean improvement of –2.75 days favoring the investigational agent at month 2.

"It is important that the headache field is aware of development of novel mechanism drugs, such as tricaprilin,” study investigator Mark Bloch, associate professor at the University of New South Wales, Sydney, said in a statement.1 "This metabolism-based option is promising and should continue in development as a possible future treatment option."

The data were presented at the recently concluded 2023 American Headache Society (AHS) Annual Meeting, held June 15-18, in Austin, Texas. Presented by Marc Cantillon, chief medical officer at Cerecin, the data only included results from the small pilot study conducted for accurate sample size calculations. Part 2 of the study, the fully powered proof-of-concept trial, was not conducted because of formulation tolerability issues.

In the study, 45.0% and 53.7% of tricaprilin and placebo-treated individuals, respectively, withdrew from the study. In addition, investigators observed similar rates of treatment-emergent adverse events (TEAEs) in both the active and placebo arms (90.0% vs 82.9%). Most TEAEs were gastrointestinal in nature.

READ MORE: Migraine Preventive Atogepant Effective in Individuals With Prior Medication Failures

Tricaprilin is a highly purified proprietary, oral formulation of a medium chain triglyceride, which has been designed to induce ketosis and thereby improve mitochondrial metabolism. The therapy is also being investigated in Alzheimer disease (AD) and other rare epilepsies. The rationale behind tricaprilin in AD is to boost cellular metabolism by providing a fuel alternative to glucose.

Cerecin registered a phase 3 trial of the therapy in AD in late 2019; however, it was withdrawn and ultimately replaced with a new study. The study aimed to enroll 300 individuals with mild to moderate AD who do not carry an apolipoprotein (APOE) e4 allele and whose FDG-PET glucose uptake pattern is typical of AD. The 26-week, double-blind, randomized, placebo-controlled, parallel-group trial uses change in Alzheimer’s Disease Assessment Scale-cognitive Subscale (ADAS-cog11) as the primary end point over a 20-week period.3

Tricaprilin is the follow-up to Accera’s AC-1202/Axona medical food product, which has been tested in several different clinical settings. In a 2009 study of 152 patients with mild to moderate AD, treatment with AC-1202 significantly elevated a serum ketone body (ß-hydroxybutryrate) 2 hours after administration when compared with placebo. Effects were most notable in individuals who did not carry the APOE e4, with a significant 4.77-point difference in mean change from baseline in ADAS-cog scores at day 45 (P = .0005) and a 3.36-point difference at day 90 (P = 0.0148) compared with placebo.4

1. Clinical trial data of novel metabolic mechanism in migraine: CER-0001, a ketogenic investigational agent. News release. June 30, 2023. July 10, 2023.
2. Chow L, Presanis J, McIntyre N, Henderson S, Cantillon M. Metabolic mechanism in migraine: trciaprilin, a ketogenic agent. Presented at: 2023 AHS Annual Meeting; June 15-18; Austin, TX. P-121.
3. A phase 3 multi regional clinical trial of tricaprilin in mild to moderately severe probable Alzheimer’s disease with optional open label extension. Updated April 14, 2023. Accessed July 10, 2023
4. Henderson ST, Vogel JL, Barr LJ, Garvin F, Jones JJ, Constantini LC. Study of ketogenic agent AC-1202 in mild to moderate Alzheimer’s disease: a randomized, double-blind, placebo-controlled, multicenter trial. Nutr Metab. 2009;6:31. doi:10.1186/1743-7075-6-31
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