The aim of this longitudinal study is to find new biological, clinical and/or electrophysiological biomarkers in order to define and differentiate individual diagnoses of NT1 and the NBL, and to find improved treatment targets and strategies.
ID
Source
Brief title
Condition
- Sleep disturbances (incl subtypes)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoints are clinical: the proportion of subjects with diagnosis
of NT1 or other CDH diagnoses at follow up. Results from this study are
expected to substantially improve (and revise) diagnostic criteria for NBL,
which may result in identification of new treatment targets/strategies.
Secondary outcome
The secondary endpoints are biological determinants and biomarkers: the
proportion of patients with autoreactive T-cell clones in NT1 and in some NBL
subjects but not in controls, and the intestinal microbiome of NT1 and NBL in
comparison to controls. The tertiary endpoints are Electrophysiological
biomarkers and questionnaire outcomes for NT1 and NBL in comparison to
controls.
Background summary
Narcolepsy type 1 (NT1) is a relatively well defined disorder with known
specific and sensitive biomarkers and a suspected autoimmune pathology. All
other central disorders of hypersomnolence (CDH) have ill-defined diagnostic
criteria with overlapping signs and symptoms and little is known about their
pathophysiology. In clinical practice excessive daytime sleepiness (EDS)
without cataplexy remains the main diagnostic challenge: Often diagnostic
criteria are only partly fulfilled and clinical signs and symptoms overlap
within the different CDH, resulting in incorrect diagnoses or even no diagnosis
can be made. As a result patients receive wrong or no treatment, even though
effective therapeutic options would exist. Therefore, a better definition of
the disorders other than NT1, the so-called narcoleptic borderland (NBL), is
urgently needed.
Study objective
The aim of this longitudinal study is to find new biological, clinical and/or
electrophysiological biomarkers in order to define and differentiate individual
diagnoses of NT1 and the NBL, and to find improved treatment targets and
strategies.
Study design
A prospective, observational, longitudinal study with 3 years follow-up for
patients and 1 year for controls. Initiated in Switzerland, with 8 Swiss
participating sleep centres. This (initially Swiss) study has been expended
internationally to Germany, Italy, and Netherlands. The Sleep-Wake Center of
SEIN is the only participating Dutch site. The data and stool samples collected
in the Dutch site are shared with the international study group. For the Dutch
site, the collected blood and CSF samples that are necessary to answer the
research questions, are collected and stored following the LUMC Narcolepsy
Biobank protocol. The few participants that did not have blood sampling within
their regular care, wil be asked to donate blood in the light on the current
research. This will be also stored following the LUMC Narcolepsy Biobank
protocol.
Study burden and risks
Biomaterial collection takes place during the regular visits in addition to the
clinical workup. Following the already existing LUMC Narcolepsy Biobank
protocol, blood and CSF that are collected within the routine clinical
procedure are stored in the biobank. The few participants that did not have
blood sampling within their regular care, wil be asked to donate blood in the
light on the current research, which is also stored in the Narcolepsy Biobank
following its protocol. For the current study, additional stool samples are
collected twice: at baseline and at the 12 month follow-up. Participants are
asked to wear a FitBit © on the wrist that monitors 24-hour activity patterns
for the duration of one year. Participants fill out a set of questionnaires at
various time points throughout their study participation, concerning disease
symptoms, psychological health, quality of life and medication adherence.
Questionnaire part A takes 5-10 minutes and is filled out 5 times (at baseline,
and at 6, 12, 24, and 36 months follow-up). Part B takes 40-50 minutes and is
filled out 3 times (at baseline, and at 12 and 36 months follow-up). A
neuropsychiatric interview is assessed twice (at baseline and at 12 month
follow-up), which takes 15-20 minutes. Patients who show signs and symptoms of
depression or acute suicidality, are given the opportunity to further evaluate
this issue during one of the clinical visits and are treated or referred if
needed. For visits which are only study-related, patients and controls will get
their travel costs refunded. Healthy controls receive ¤150 (divided over four
time points) for their study participation.
Achterweg 3
Heemstede 2105 SW
NL
Achterweg 3
Heemstede 2105 SW
NL
Listed location countries
Age
Inclusion criteria
All participants:
- Age 16-70 years
- Ability and consent to undergo electrophysiological routine assessment
- Ability to give informed consent
Patients:
- Subjective complaints of excessive daytime sleepiness (EDS) and/or
hypersomnolence (H) as defined in the protocol
- EDS and/or H present daily or almost daily for at least 1 month prior to the
consultation
Healthy Controls:
- Proportionally age and gender matched healthy subjects
Exclusion criteria
All participants:
- Chronic infectious diseases (such as Hepatitis B/C, HIV)
- Chronic use of antibiotics
- Recent use (over 8 weeks) of immune-modulating drugs
Patients:
- The following disorders/conditions that on clinical grounds are considered to
be the cause of EDS/H:
-- Other sleep disorders
-- Other neurological disorders
-- (Auto-)immune and systemic disorders
-- Malignancy (except: Status in Remission for over 10 years)
-- Instable psychiatric disorder
-- Active infectious disease at screening
-- Permanent medications/drugs
- Sleep disordered breathing (SDB): Presence of clinically significant and
untreated obstructive (OSA) or central sleep apnea (CSA) as determined by the
investigator or documented previously; or documentation of one of the
following:
-- Apnea index (AI) over10 if on OSA treatment or untreated; or
-- Clinically significant hypoventilation; or
-- Noncompliance with primary OSA/PAP therapy in case of clinically
significant OSA
-- except if NTI has been diagnosed including decreased or missing CSF
hypocretin
Healthy Controls:
- Subjective complaints of EDS and/or H as defined in the protocol
- Epworth Sleepines Scale (ESS) over 10
- Polysomnography (PSG) with apnea index (AI) over10/h and/or periodic leg
movement series (PLMS) Index over 30/h
- SDB: Presence of clinically significant and untreated OSA or central sleep
apnea (CSA) as determined by the investigator or documented previously; or
documentation of one of the following:
-- Apnea index (AI) over 10 if on OSA treatment or untreated; or
-- Clinically significant hypoventilation; or
-- Noncompliance with primary OSA/PAP therapy
Design
Recruitment
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
CCMO | NL84710.058.23 |