Clinical trial NCT07006233: A Novel Approach to Manage Symptoms of Narcolepsy and Idiopathic Hypersomnia
Official title: A Novel Dietary Approach to Manage Symptoms of Narcolepsy and Idiopathic Hypersomnia
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Idiopathic Hypersomnia
Narcolepsy Type 1 (NT 1)
Narcolepsy Type 2 (NT2)
Keywords: keto diet
ketogenic
keto
whole food diet
narcolepsy
idiopathic hypersomnia
low carb
hypersomnolence
diet
dietary intervention
diet intervention
Lead sponsor: University of Sydney
Sponsor class: OTHER
Collaborators: name: Woolcock Institute of Medical Research
First posted: 2025-06-05
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A prospective mixed methods clinician led randomised controlled hybrid type 1 study
Primary purpose: TREATMENT

Brief summary: The aim of this project is to learn about how a change in diet will affect sleepiness, quality of life and metabolic health in people living with narcolepsy and idiopathic hypersomnia. The dietary changes we will be testing are well researched and safe in a wide range of patient groups (such as in obesity, type one and two diabetes, cancer and dysfunction related to the nervous system) but has not been researched in conditions of hypersomnolence such as narcolepsy and idiopathic hypersomnia. It is important to test adjunct therapies and lifestyle changes such as dietary interventions to ensure that people living with hypersomnolence have a range of options in addition to medications, to improve their health.

If effective, this project will be tested in more people and may become a part of routine patient care. These dietary approaches have been shown to improve health and quality of life in people living with chronic pain, neurological conditions such as epilepsy and have been shown to be safe in these populations as well as people living with type one diabetes. This is a new area of research for people living with hypersomnolence.

Detailed description: The primary objectives of COMPANION are:

• To determine the feasibility and tolerability of a 12-week whole-food ketogenic diet (WFKD) compared to an isocaloric standard whole-food diet (WFD) in participants with hypersomnolence (HS) as defined by the RE-AIM Framework.

The secondary objectives are:

* To determine whether a WFKD achieves greater improvements in disease relevant sleep outcomes including excessive daytime sleepiness, reduced duration of sleep onset latency and psychomotor vigilance compared to an isocaloric WFD in participants with HS.
* To determine whether a WFKD achieves greater improvements in objective metabolic health outcomes and subjective quality of life outcomes compared to an isocaloric WFD in participants with HS.
* To determine whether patients prefer a combination of dietary intervention and medication or unique dietary intervention compared to traditional medication only treatments in their lived experience.
* To better understand the context for implementation of both dietary interventions, determining the barriers and facilitators to widespread implementation of the dietary intervention.

A prospective, mixed methods, randomised, single-centre, controlled trial (Hybrid Type 1) with two parallel groups comparing the feasibility of a WFKD to a WFD stratified by patient diagnosis of NT1, NT2 or IH. This project will determine whether patients with persistent HS can feasibly sustain dietary changes in addition to usual care, and if so, whether improvements in symptoms of daytime sleepiness, metabolic health and quality of life outcomes can be enhanced with a WFKD. At the core of this project is the delivery of a 12-week dietary intervention, in which all patients will be initially allocated to a WFD for three weeks. At the commencement of week four, participants will be randomised to either maintain consumption of this WFD or combine with carbohydrate restriction to form a WFKD for the remaining nine weeks.

The inclusion of a three-week run-in period for all patients provides confidence to the design that patients entering randomisation can engage with dietary change, and thus will provide our first indicator of feasibility. The WFD group from this point on will serve as a comparator in this randomised clinical trial.

Eligibility criteria: Inclusion Criteria:

* Evidence (from multiple sleep latency test, 24-hour polysomnography, or actigraphy) of diagnosis of narcolepsy type 1, narcolepsy type 2 or idiopathic hypersomnia that meets ICSD-3 criteria.
* For the NT1 subtype, patients must have been screened positive for the HLA DQB10602 genotype.
* Body mass index \>18.5 kg/m2
* 18 years or over
* Be willing to be involved in dietary change that may include animal protein and fat.
* Be willing to monitor ketones via finger-prick and urinary dipstick.
* Habitual diet is a standard diet consuming a moderate or high carbohydrate level (defined for the study as above 130g carbohydrate/day).
* Willingness to provide informed consent and willingness to participate and comply with the study requirements.
* Access to a computer, laptop, tablet, or smartphone and stable internet access.
* Proficient comprehension of English language (able to independently read information sheet) and availability of a support person during consultations if English comprehension is challenged.

Exclusion Criteria:

* Body mass index \<18.5 kg/m2, history of an eating disorder with an EDE-Q score greater than 3.
* Participants who have sustained significant weight loss in the last 3 months (\>5% change in total body weight).
* Previous bariatric surgery or current prescription of weight loss medication.
* Diagnosis of unstable psychiatric disorders (excluding anxiety or depression).
* Cognitive impairment that limits ability to understand the study requirements or provide informed consent.
* Physical impairment that limits ability to meet the study requirements.
* Non-English speaking and inability to read the Participant Information Sheet.
* No access to stable internet and device on which to participate in telehealth consultations and complete study questionnaires.
* Person lactating, pregnant or of childbearing potential who are not willing to avoid becoming pregnant during the study period.
* Habitual diet is currently low carbohydrate/ketogenic (defined for the study as \<130g carbohydrate/day based on screening 24 food hour recall).
* Habitual diet excludes animal products (e.g. Vegan diet).
* Laboratory parameters that may indicate alternate catalyst for hypersomnolence in the opinion of the study physician, including abnormal: full blood count, thyroid function, Epstein-Barr Virus, erythrocyte sedimentation rate, cortisol, antinuclear antibodies, extractable nuclear antigen test, positive rheumatoid factor, Antistreptolysin O positive, Iron studies or multiple biochemistry panel.
* Participants who have changed their medication prescription or dose within the preceding 4 weeks.
* Participants with inherited metabolic disorders, prior history of hypoglycaemia or insulinoma
* Participants with insulin dependent Type 1 or Type 2 diabetics prescribed insulin which may interfere with the participant's ability to meet the study requirements.
* Participants with uncontrolled medical conditions or patients with significant medical co-morbidities who in the opinion of the study physician, would be at risk of adverse health consequences due to the study intervention (e.g. poorly controlled type 2 diabetic patients who are not prescribed insulin)
* Current cancer diagnosis (excluding skin cancers or benign cancers)
* Current active enrolment in a pharmaceutical or intervention based clinical trial or participant who may have received an investigational new drug within the last 12 weeks.

Primary outcomes:
measure: Feasibility - using quantitative measures of feasibility
timeFrame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
measure: Feasibility - using quantitative measures of tolerability
timeFrame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
measure: Feasibility - using quantitative measures of compliance
timeFrame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
Secondary outcomes:
measure: Sleep Outcomes - average sleep onset latency
timeFrame: From baseline visit in week 0 to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
measure: Sleep Outcomes - markers of sleep micro-architecture
timeFrame: From baseline visit in week 0 to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
measure: Sleep Outcomes - Narcolepsy Severity Scale (for NT1 and NT2)
timeFrame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
measure: Sleep Outcomes - Idiopathic Hypersomnia Severity Scale (for IH)
timeFrame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
measure: Sleep Outcomes - weekly cataplexy rate
timeFrame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
measure: Sleep Outcomes - Karolinska Sleepiness Scale
timeFrame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
measure: Sleep Outcomes - Epworth Sleepiness Scale
timeFrame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
measure: Sleep Outcomes - Psychomotor Vigilance Task (PVT)
timeFrame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
measure: Exploratory Sleep Outcomes - quantitative analysis of the EEG from PSG data
timeFrame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
measure: Cardio-metabolic and Quality of Life Outcomes - high sensitivity C-reactive protein (hs-CRP)
timeFrame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
measure: Cardio-metabolic and Quality of Life Outcomes - 36-Item Short Form Survey summary scores
timeFrame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
measure: Cardio-metabolic and Quality of Life Outcomes - laboratory blood analyses
timeFrame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
measure: Cardio-metabolic & Quality of Life Outcomes - anthropometry and vitals data
timeFrame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
measure: Cardio-metabolic & Quality of Life Outcomes - assessment of mood and quality of life using 36-Item Short Form Survey
timeFrame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
measure: Cardio-metabolic & Quality of Life Outcomes - assessment of mood and quality of life using Hospital Anxiety and Depression Scale
timeFrame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
measure: Cardio-metabolic & Quality of Life Outcomes - assessment of mood and quality of life using EQ-5D-5L
timeFrame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
measure: Cardio-metabolic & Quality of Life Outcomes - assessment of mood and quality of life using Clinical Global Impression
timeFrame: At the end of 12 weeks for the last enrolled participant.
measure: Demographics & diagnostic history
timeFrame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
measure: Adherence and lived experience during intervention - diet satisfaction
timeFrame: From the end of 3 weeks to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
measure: Adherence and lived experience during intervention - macronutrient/micronutrient change
timeFrame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
measure: Adherence and lived experience during intervention - dietary adherence measured by blood ketosis level
timeFrame: From the baseline visit in week 0 to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
measure: Adherence and lived experience during intervention - dietary adherence measured by urine ketosis level
timeFrame: From the baseline visit in week 0 to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
measure: Adherence and lived experience during intervention - habitual actigraphy sleep-wake data
timeFrame: From week -1 to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
measure: Adherence and lived experience during intervention - habitual sleep diary sleep-wake data
timeFrame: From week -1 to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
measure: Adherence and lived experience during intervention - Patient Reported Experience Measures - Longitudinal PREM
timeFrame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
measure: Adherence and lived experience during intervention - Patient Reported Experience Measures - Patient Assessment of Chronic Illness Care
timeFrame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
measure: Adherence and lived experience during intervention - Patient Reported Experience Measures - Outpatient PREM
timeFrame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
measure: Qualitative Data - semi-structured interviews
timeFrame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
measure: Qualitative Data - overall project evaluation
timeFrame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.
Other outcomes:
Locations:
city: Macquarie Park
country: Australia
facility: Woolcock Institute of Medical Research
state: New South Wales
Study officials:
affiliation: University of Sydney
name: Elizabeth A Machan, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal Prince Alfred Hospital and University of Sydney
name: Sheila Sivam, PhD; MD; FracP; BSc (Med)
role: PRINCIPAL_INVESTIGATOR
References: