Re-evaluating the placebo response in recent canine dietary epilepsy trials.

The placebo response is a common phenomenon. Limited evidence is available about its magnitude in canine epilepsy trials, even though it can significantly influence the efficacy evaluation of new treatments. It was hypothesised that the placebo response is diminished when epilepsy trials are conducted in a prospective crossover design. Seizure data spanning six months from three previous multicenter epilepsy studies were analysed. The monthly seizure frequency of 60 dogs diagnosed with idiopathic epilepsy was calculated, comparing baseline data with placebo treatment. Furthermore, differentiation was made between dogs randomised to the placebo group early (Phase 1: first 3 months) or later during the study (Phase 2: second 3 months).The analysis did not reveal any placebo response in terms of monthly seizure frequency. Instead, an increase was noted during the placebo treatment period, with a mean of 2.95 seizures per month compared to 2.30 seizures per month before study entry (p = 0.0378). Additionally, a notable phase effect was observed. Dogs receiving the placebo in the second study phase exhibited a significant increase in monthly seizure frequency compared to baseline (p = 0.0036). Conversely, no significant difference from baseline was observed for dogs receiving the placebo in the first study phase. These findings underscore the considerable variability in placebo responses observed in trials for canine epilepsy, contrasting with previous limited data. The identified phase effect should be carefully considered in the design and evaluation of canine epilepsy trials to ensure a more accurate assessment of efficacy for new treatments.

Urinary Neurotransmitter Patterns Are Altered in Canine Epilepsy.

Epilepsy is the most common chronic neurological disease in humans and dogs. Epilepsy is thought to be caused by an imbalance of excitatory and inhibitory neurotransmission. Intact neurotransmitters are transported from the central nervous system to the periphery, from where they are subsequently excreted through the urine. In human medicine, non-invasive urinary neurotransmitter analysis is used to manage psychological diseases, but not as yet for epilepsy. The current study aimed to investigate if urinary neurotransmitter profiles differ between dogs with epilepsy and healthy controls. A total of 223 urine samples were analysed from 63 dogs diagnosed with idiopathic epilepsy and 127 control dogs without epilepsy. The quantification of nine urinary neurotransmitters was performed utilising mass spectrometry technology. A significant difference between urinary neurotransmitter levels (glycine, serotonin, norepinephrine/epinephrine ratio, ɤ-aminobutyric acid/glutamate ratio) of dogs diagnosed with idiopathic epilepsy and the control group was found, when sex and neutering status were accounted for. Furthermore, an influence of antiseizure drug treatment upon the urinary neurotransmitter profile of serotonin and ɤ-aminobutyric acid concentration was revealed. This study demonstrated that the imbalances in the neurotransmitter system that causes epileptic seizures also leads to altered neurotransmitter elimination in the urine of affected dogs. Urinary neurotransmitters have the potential to serve as valuable biomarkers for diagnostics and treatment monitoring in canine epilepsy. However, more research on this topic needs to be undertaken to understand better the association between neurotransmitter deviations in the brain and urine neurotransmitter concentrations in dogs with idiopathic epilepsy.

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

BACKGROUND: Medium-chain triglyceride (MCT) enriched diet has a positive effect on seizure control and behavior in some dogs with idiopathic epilepsy (IE). OBJECTIVE: To evaluate the short-term efficacy of MCTs administered as an add-on dietary supplement (DS) to a variable base diet to assess seizure control and antiseizure drug's (ASD) adverse effect profiles. ANIMALS: Twenty-eight dogs with International Veterinary Epilepsy Task Force Tier II (IVETF) level diagnosis of treated IE with 3 or more seizures in the last 3 months were used. METHODS: A 6-month multicenter, prospective, randomized, double-blinded, placebo-controlled crossover trial was completed, comparing an MCT-DS with a control-DS. A 9% metabolic energy-based amount of MCT or control oil was supplemented to the dogs' diet for 3 months, followed by a control oil or MCT for another 3 months, respectively. Dogs enrolled in this study satisfied most requirements of IE diagnosis stated by the IVETF II level. If they received an oil DS or drugs that could influence the metabolism of the investigated DS or chronic ASD, the chronic ASD medication was adjusted, or other causes of epilepsy were found, the dogs were excluded from the study. RESULTS: Seizure frequency (median 2.51/month [0-6.67] versus 2.67/month [0-10.45]; P = .02) and seizure-day frequency were significantly (1.68/month [0-5.60] versus 1.99/month [0-7.42], P = .01) lower when dogs were fed MCT-DS in comparison with the control-DS. Two dogs were free of seizures, 3 had ≥50% and 12 had <50% reductions in seizure frequency, and 11 dogs showed no change or an increase in seizure frequency. CONCLUSIONS AND CLINICAL IMPORTANCE: These data show antiseizure properties of an MCT-DS compared to a control oil and support former evidence for the efficacy of MCTs as a nutritive, management option for a subpopulation of drug-resistant dogs with epilepsy.