Effectiveness of ketogenic diet on excessive daytime sleepiness in adults with narcolepsy type 1: a proof of concept study

Narcolepsy type 1 (NT1) is a rare neurologic sleep-wake disorder, caused by
hypocretin insufficiency. It is characterized by various invalidating symptoms,
such as an inability to stay awake during the day, an inability to stay asleep
at night, excessive daytime sleepiness (EDS), difficulty with alertness,
vigilance, attention, concentration, and they often experience sudden loss of
muscle tonus after a strong emotion (cataplexy), hypnagogic hallucinations, and
sleep paralysis. Moreover, patients with NT1 complain about memory
difficulties, automatic behavior, tiredness, mood and depressive symptoms,
anxiety, and they often become overweight or obese in the first stage of
developing NT1. Currently, the most effective treatment for the symptoms of NT1
is medication and lifestyle advice, such as taking regular naps during the day.
Our clinical experience indicates that minimizing carbohydrate intake may
reduce EDS, and also helps them stay alert or to have a better focus for longer
periods of time during the day. Previous research showed that a ketogenic diet
(KD) (a low/non-carbohydrate diet) had a positive effect on self-reported EDS
in a group of patients with NT1.

This study comprises a first proof of concept. The primary aim is to
investigate the effect of a ketogenic diet on EDS and sustained attention in
adult NT1 patients. Secondary aims are to investigate if a ketogenic diet
improves weight reduction, any improvements in sleep during the night and
adherence to a ketogenic diet in narcolepsy type 1 patients.

Proof-of-concept (pilot) intervention study.

All participants follow a ketogenic diet as instructed and monitored by a
certified dietician for 12 weeks. Then participants are asked to continue the
diet without guidance by a dietician. Outcomes are measured at baseline (week
1), at the end of the guided diet (week 13), and at study end (week 25). Prior
to each measurement participants will wear actigraphy, measuring sleep and wake
periodes by movement and light. ketones in blood and/or urine samples are
monitored during the study in order to evaluate if the diet intervention has
succeeded.

Participants are asked to visit the study site (SEIN, Heemstede) five times;
twice at baseline, twice at week 13 and once at week 25. The fist visits in
weeks 1 and 13 will take 45-60 minutes, and involves the attachment of the
electrodes and sensors to the head, face, and on the body of the participant.
On full study days in weeks 1, 13, and 25, various tests will be done (MWT,
SART), blood is drawn (fingertip blood sample), questionnaires are filled out,
physical measurements (weight, fat%) are done. Participants will also have an
interview with the dietician. Between baseline and week 13, participants
regularly have contact with the dietician by telephone or e-mail. Throughout
the study participants will verify if they are in a state of ketosis via
urinary strips measuring ketones.