Clinical and Neurophysiological Characteristics of Narcolepsy

Clinical and Neurophysiological Characteristics of Narcolepsy in Russia Basing on Clinical, Polysomnographic and Genome-wide Association Analyses of Narcolepsy With Cataplexy: a European Narcolepsy Network Study of 2013

The study is the first attempt in post-Soviet Russian history to collect and analyze the existing available data of narcolepsy cohort in order to get prove characteristics of narcolepsy in Russia according to known data. Investigators created the system of national narcolepsy centers in Russia - Russian narcolepsy network, with a purpose of collecting clinical and neurophysiological data with subsequent analyze and formation of Russian narcolepsy profile.

Study Overview

• Status: Completed
• Conditions: Narcolepsy Type 1
• Intervention / Treatment: Other: no intervention

Detailed Description

First reports of narcolepsy with cataplexy in Russia were made by Mankovsky in 1925 (narcolepsy with cataplexy, NC). The largest series of patients (n=110) was reported by A. Vein in 1964. Narcolepsy remains however until today relatively unknown in Russia. The aim of this study is to report clinical and polysomnographic (PSG)/multiple sleep latency test (MSLT) results in a Russian population and compare them with the European narcolepsy network (n=1099) reported (Luca G, Haba-Rubio J, Dauvilliers Y, Lammers GJ, Overeem S, Donjacour CE, Mayer G, Javidi S, Iranzo A, Santamaria J, Peraita-Adrados R, Hor H, Kutalik Z, Plazzi G, Poli F, Pizza F, Arnulf I, Lecendreux M, Bassetti C, Mathis J, Heinzer R, Jennum P, Knudsen S, Geisler P, Wierzbicka A, Feketeova E, Pfister C, Khatami R, Baumann C, Tafti M; European Narcolepsy Network. Clinical, polysomnographic and genome-wide association analyses of narcolepsy with cataplexy: a European Narcolepsy Network study. J Sleep Res. 2013 Oct;22(5):482-95. doi: 10.1111/jsr.12044. Epub 2013 Mar 18. PMID: 23496005., 2013).

For the purpose of this study only patients with narcolepsy with cataplexy were considered because of the uncertainty about the diagnosis of narcolepsy without cataplexy.

In order to create a network of sleep centers with expertise/interest in narcolepsy 79 centers from 27 Russian cities were connected in 2019. A total of 11 centers officially joined the Russian Narcolepsy Network (rnane.ru) and agreed to participate in the current study. A standardized questionnaire, similar to the one reported by the EU-NN in a series of 1099 patients (Luca G, Haba-Rubio J, Dauvilliers Y, Lammers GJ, Overeem S, Donjacour CE, Mayer G, Javidi S, Iranzo A, Santamaria J, Peraita-Adrados R, Hor H, Kutalik Z, Plazzi G, Poli F, Pizza F, Arnulf I, Lecendreux M, Bassetti C, Mathis J, Heinzer R, Jennum P, Knudsen S, Geisler P, Wierzbicka A, Feketeova E, Pfister C, Khatami R, Baumann C, Tafti M; European Narcolepsy Network. Clinical, polysomnographic and genome-wide association analyses of narcolepsy with cataplexy: a European Narcolepsy Network study. J Sleep Res. 2013 Oct;22(5):482-95. doi: 10.1111/jsr.12044. Epub 2013 Mar 18. PMID: 23496005., 2013) was sent by mail to the 11 centers. The questionnaire included the following parameters:

1. Demographic characteristics: date of birth, gender, height, weight, BMI(body mass index) at diagnosis.
2. Age at EDS (excessive daytime sleepines) onset and age at cataplexy onset. Investigators defined the age at onset of NC(narcolepsy with cataplexy) as the age at occurrence of EDS and/or cataplexy, determined during the clinical interview.
3. Frequency of cataplexy attacks at diagnosis. The frequency of cataplexy was assessed by a scale from 1 to 5, reporting rare to very frequent cataplexy attacks: 1 = one or less cataplexy attacks per year; 2 = more than one cataplexy attack per year but less than one per month; 3 = more than one attack per month but less than one per week; 4 = more than one per week but less than one per day; 5 = at least one cataplexy attack per day.
4. ESS (Epworth Sleepiness Scale) score at diagnosis.
5. Polysomnographic variables [sleep onset latency at diagnosis, apnea-hypopnea index (AHI) and periodic leg movements during sleep index (PLMSI) when available] and MSLT results (mean sleep latency, number of SOREMPs) at diagnosis. Even if the recording procedures were different among centers, most of the patients underwent nocturnal in-lab PSG followed by an MSLT as part of the diagnostic evaluation. For PSG and MSLT, sleep latency was defined as the time from lights off to the first epoch scored as sleep. A SOREMP was defined as the occurrence of an epoch of REM(rapid eye movement) sleep within 15 min after the first epoch scored as sleep. Although MSLT was performed according to standard methods (Carskadon MA, Dement WC, Mitler MM, Roth T, Westbrook PR, Keenan S. Guidelines for the multiple sleep latency test (MSLT): a standard measure of sleepiness. Sleep. 1986 Dec;9(4):519-24. doi: 10.1093/sleep/9.4.519. PMID: 3809866.), the number of scheduled naps could be variable. To standardize the results, investigators calculated the percentage of SOREMPs of the total number of naps: percentage of naps with SOREMPs.

7. Associated features, with particular attention to symptoms frequently reported with narcolepsy: sleep paralysis (SP); hypnagogic/hypnopompic hallucinations (HH); and poor nocturnal sleep.

8. Co-morbidities (sleep-related, somatic or psychiatric) and treatment when available.

• Study Type: Observational
• Enrollment (Actual): 89

Contacts and Locations

Study Locations

• Russian Federation
  • Chelyabinsk, Russian Federation
    • Regional Clinical Hospital No.3
  • Kazan, Russian Federation
    • Kazan State Medical University
  • Khabarovsk, Russian Federation
    • Private healthcare institution 'Clinical hospital 'RZD-Medicine'
  • Moscow, Russian Federation
    • I.M. Sechenov First Moscow State Medical University (Sechenov University)
  • Moscow, Russian Federation
    • Burnasyan federal medical biophysical center of federal medical biological agency
  • Moscow, Russian Federation
    • FSBI NMRCO FMBA Russia
  • Novosibirsk, Russian Federation
    • Novosibirsk State Medical University
  • Saint Petersburg, Russian Federation
    • Almazov National Medical Research Centre
  • Saint Petersburg, Russian Federation
    • Nikiforov Russian Center of Emergency and Radiation Medicine, EMERCOM of Russia
  • Saint Petersburg, Russian Federation
    • V. M. Bekhterev National Research Medical Center for Psychiatry and Neurology
  • Samara, Russian Federation
    • Samara State Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 78 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Men and women aged 6-80 who have been diagnosed with narcolepsy type I, met inclusion criteria and who(or whose representatives in case of being under 18 years) agreed to participate in studying.

Description

Inclusion Criteria:

1. Signed written informed consent of the patient and/or parent/adoptive parent (in the case of a minor) to participate in the study;
2. Age: 6-80 years;
3. Gender: Men and women;
4. Established diagnosis: Narcolepsy of type I and II (according to the criteria of the International classification of sleep disorders of 2014).

Exclusion Criteria:

1. Refusal of the patient or his parent / adoptive parent (in the case of a minor) from further participation in the study;
2. The occurrence of a serious illness or a significant deterioration of a disease unrelated to narcolepsy;
3. Pregnancy started after inclusion.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
date of birth	year of birth	during 1-3 years after beginning and when patient and data are available
gender	male or female	during 1-3 years after beginning and when patient and data are available
height	meters	during 1-3 years after beginning and when patient and data are available
weight	kilograms	during 1-3 years after beginning and when patient and data are available
BMI at diagnosis	Weight and height will be combined to report BMI in kg/m^2 at the time of diagnosis	during 1-3 years after beginning and when patient and data are available
age at EDS (excessive daytime sleepioness) onset	Age when EDS first time was reported by patient	during 1-3 years after beginning and when patient and data are available
age at cataplexy onset	Age when cataplexy first time was reported by patient	during 1-3 years after beginning and when patient and data are available
frequency of cataplexy attacks at diagnosis	Reported at diagnosis. The frequency of cataplexy was assessed by a scale from 1 to 5, reporting rare to very frequent cataplexy attacks: 1 = one or less cataplexy attacks per year; 2 = more than one cataplexy attack per year but less than one per month; 3 = more than one attack per month but less than one per week; 4 = more than one per week but less than one per day; 5 = at least one cataplexy attack per day.	during 1-3 years after beginning and when patient and data are available
ESS score at diagnosis	Unit of Measure at diagnosis	during 1-3 years after beginning and when patient and data are available
Apnea-hypopnea index (AHI)	PSG at diagnosis, Unit of Measure at diagnosis	during 1-3 years after beginning and when patient and data are available
Periodic leg movements during sleep index (PLMSI)	Number of episodes and hours of sleep combined to report PLMSI in episodes per hour.	during 1-3 years after beginning and when patient and data are available
Sleep onset latency at diagnosis	Time from lights off to the first epoch scored as sleep in PSG. Measured in minutes.	during 1-3 years after beginning and when patient and data are available
Sleep latency	Time from lights off to the first epoch scored as sleep in MSLT. Measured in minutes.	during 1-3 years after beginning and when patient and data are available
Number of SOREM	It was defined as the occurrence of an epoch of REM sleep within 15 min after the first epoch scored as sleep. Then investigators calculated the percentage of SOREMPs of the total number of naps: percentage of naps with SOREMPs.	during 1-3 years after beginning and when patient and data are available
Frequently of sleep paralysis, hypnagogic/hypnopompic hallucinations and poor nocturnal sleep, co-morbidities (sleep-related, somatic or psychiatric) and treatment when available.	Percentage of occurence in group.	during 1-3 years after beginning and when patient and data are available

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
summarization of collected database with European one	analyzing and comparison collected data with European one leading to final summarization of studying	1 year after receiving data from sleep centers from Russia and publishing results

Collaborators and Investigators

• Sponsor: I.M. Sechenov First Moscow State Medical University
• Investigators: Principal Investigator: Alexander Kuts, I.M. Sechenov First Moscow State Medical University (Sechenov University)

Publications and helpful links

General Publications

• Kuts A, Poluektov M, Bassetti CLA. The evolution of the narcolepsy concept in Russia: A historical view. J Hist Neurosci. 2021 Apr-Jun;30(2):113-127. doi: 10.1080/0964704X.2020.1777502. Epub 2020 Jun 30.
• Kuts A, Poluektov M, Zakharov A, Govzman V, Ponomareva I, Yakupov E, Zavalko I, Tikhomirova O, Sviryaev Y, Yakovlev A, Polyakov A, Melnikov A, Bassetti CLA. Clinical and neurophysiological characteristics of 89 patients with narcolepsy and cataplexy from the Russian Narcolepsy Network. J Clin Sleep Med. 2023 Feb 1;19(2):355-359. doi: 10.5664/jcsm.10340.

Helpful Links

• Official website of Russian narcolepsy network

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2019
• Primary Completion (Actual): February 1, 2022
• Study Completion (Actual): September 28, 2023

Study Registration Dates

• First Submitted: May 4, 2022
• First Submitted That Met QC Criteria: May 12, 2022
• First Posted (Actual): May 17, 2022

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Russia; PSG; narcolepsy; cataplexy; MSLT; excessive sleepiness
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Disorders of Excessive Somnolence; Narcolepsy
• Other Study ID Numbers: 246188

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD Sharing can be done after written official request in Sechenov University and approval of Central Contact investigator because our local Ethics committee does not allow free study sharing.
• IPD Sharing Time Frame: After official request and approval the data will become available with an indication of the terms of use.
• IPD Sharing Access Criteria: Our Ethics committee does not approve free study sharing. We can provide it only after written official request in Sechenov University and approval of Central Contact investigator.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No