A double-blinded randomised dietary supplement crossover trial design to investigate the short-term influence of medium chain fatty acid (MCT) supplement on canine idiopathic epilepsy: study protocol

Abstract

Background Epilepsy is the most common brain disease in dogs. Recently, diets have been reported to have a positive impact on seizure activity and behaviour in various species including dogs with idiopathic epilepsy (IE). Historically, classic high fat ketogenic diets (KD) and medium chain triglycerides (MCT) KD have been successfully used to manage drug-resistant epilepsy. Similarly, an MCT enriched diet has been shown to improve seizure control and behavioural comorbidities in some dogs with IE. However, it is unknown whether an MCT dietary supplement (DS) may provide similar positive effects. Methods A 6-month prospective, randomised, double-blinded, placebo-controlled, crossover, multicentre dietary trial is designed comparing a 9% metabolic energy based calculated medium-chain triglyceride (MCT) oil supplement to a conventional ‘control’ DS. Only dogs which will have an International Veterinary Epilepsy Task Force Tier II level like diagnosis of IE which satisfied the following inclusion criteria are included: age between 6 months and ≤ 12 years; weighing between 4 and ≤ 65 kg; unremarkable interictal neurological examinations; no clinically significant findings on routine laboratory diagnostics; unremarkable brain MRI scan; have had at least 3 seizures in the previous 3 months prior to enrolment; treated with at least one ASD and being classified as resistant. All dogs are fed initially for 90 ± 2 days with either the control oil or the MCT oil alongside their normal diet, followed by 97 ± 2 days with the other supplement including a 7-day washout period. Overall, the aim is to recruit thirty-six patients at five different centres and to investigate the effect of MCTs as DS on seizure activity, tolerability, behavioural comorbidities and quality of life (QoL). Discussion Dietary interventions are rarely studied in a standardised form in veterinary medicine. The background diet, the cohort of animals and ASD received is standardised in this prospective diet trial to ensure representative data about the potential effect of MCT DS. If the study data confirms former findings, this would provide further evidence for the efficacy of MCTs as a management option for canine epilepsy. This publication should offer a repository of trial conditions and variable description with forecasted statistical analysis. Electronic supplementary material The online version of this article (10.1186/s12917-019-1915-8) contains supplementary material, which is available to authorized users.

A multicenter randomized controlled trial of medium‐chain triglyceride dietary supplementation on epilepsy in dogs

“…The study design has been published separately 44 . In brief, the main study hypothesis was that MCTs administered as a DS would reduce seizure frequency.…”

Dietary medium chain triglycerides for management of epilepsy: New data from human, dog, and rodent studies

“…Nine of 21 dogs (43%) had more than 50% reduction in seizure frequency, including two dogs becoming seizure‐free 101 . In a recently published multicenter randomized double‐blinded crossover study, dog owners were taught to add MCT oil (contributing 9% daily energy) containing 50%–65% octanoate and 30%–50% decanoate versus colorless, extra virgin olive oil to their dogs' regular food for a total of 28 dogs 102,103 . The case number chosen for this study was based on the results of Law et al, 99 who used a similar study design 102,103 .…”

“… 101 In a recently published multicenter randomized double‐blinded crossover study, dog owners were taught to add MCT oil (contributing 9% daily energy) containing 50%–65% octanoate and 30%–50% decanoate versus colorless, extra virgin olive oil to their dogs' regular food for a total of 28 dogs. 102 , 103 The case number chosen for this study was based on the results of Law et al, 99 who used a similar study design. 102 , 103 A power analysis was performed and indicated that 22 dogs would be sufficient using Wilcoxon signed ranked test to reach a power of .95 (90%) at Type I error rate of .05 (PASS V19.02, NCSS, Statistical Software).…”

“… 102 , 103 The case number chosen for this study was based on the results of Law et al, 99 who used a similar study design. 102 , 103 A power analysis was performed and indicated that 22 dogs would be sufficient using Wilcoxon signed ranked test to reach a power of .95 (90%) at Type I error rate of .05 (PASS V19.02, NCSS, Statistical Software). Overall, there was a significant 22% reduction in the median number of seizures with add‐on MCT feeding.…”

Probable Sudden Unexpected Death in Dogs With Epilepsy (pSUDED)

“…Around 0.6% of the dog population and up to 18.3% of dogs of specific breeds are affected by epilepsy (14)(15)(16). There are several studies about quality of life (QoL) in canine patients with epilepsy (17)(18)(19)(20), but sudden unexpected death in dogs is only sporadically reported and poorly studied (21)(22)(23)(24). Idiopathic epilepsy (IE) is described as an exclusion diagnosis for dogs of a certain age group with recurrent seizures without an underlying structural cause, but with a (presumed) genetic influence (25,26).…”