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

Overview

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.

Interventions

• Behavioral Whole Food Ketogenic Diet
  Education around immediate changes to improve diet quality and barriers to dietary behaviour change. Participants will consume a whole-food diet focused on improving diet quality based on the NOVA classifications of unprocessed or minimally processed foods/ingredients (removal of NOVA category 4 foods from diet). This group will focus on the consumption of low-energy, nutrient dense whole foods with a targeted carbohydrate intake of 30-50g per day to achieve nutritional ketosis. The WFKD will ad
• Behavioral Whole Food Diet
  Education around immediate changes to improve diet quality and barriers to dietary behaviour change. Participants will consume a whole-food diet focused on improving diet quality based on the NOVA classifications of unprocessed or minimally processed foods/ingredients (removal of NOVA category 4 foods from diet). This diet is high carbohydrate (45-65% of total energy coming from carbohydrate, 20-35% from fat and 15-25% from protein) based on the Australian dietary guidelines focusing on the cons

Primary outcome measures

• Feasibility - using quantitative measures of feasibility [Time frame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.]
• Feasibility - using quantitative measures of tolerability [Time frame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.]
• Feasibility - using quantitative measures of compliance [Time frame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.]

Secondary outcome measures (12)

• Sleep Outcomes - average sleep onset latency [Time frame: 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.]
• Sleep Outcomes - markers of sleep micro-architecture [Time frame: 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.]
• Sleep Outcomes - Narcolepsy Severity Scale (for NT1 and NT2) [Time frame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.]
• Sleep Outcomes - Idiopathic Hypersomnia Severity Scale (for IH) [Time frame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.]
• Sleep Outcomes - weekly cataplexy rate [Time frame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.]
• Sleep Outcomes - Karolinska Sleepiness Scale [Time frame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.]
• Sleep Outcomes - Epworth Sleepiness Scale [Time frame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.]
• Sleep Outcomes - Psychomotor Vigilance Task (PVT) [Time frame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.]
• Exploratory Sleep Outcomes - quantitative analysis of the EEG from PSG data [Time frame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.]
• Cardio-metabolic and Quality of Life Outcomes - high sensitivity C-reactive protein (hs-CRP) [Time frame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.]
• Cardio-metabolic and Quality of Life Outcomes - 36-Item Short Form Survey summary scores [Time frame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.]
• Cardio-metabolic and Quality of Life Outcomes - laboratory blood analyses [Time frame: From enrolment to the completion of the last study visit at the end of 12 weeks for the last enrolled participant.]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Australia · 1 center

• Woolcock Institute of Medical Research — Macquarie Park

Identifiers

NCT: NCT07006233 · COMPANION · 316-SR-23

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗