Risk of Narcolepsy Associated With Administration of H1N1 Vaccine
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|ClinicalTrials.gov Identifier: NCT01394614|
Recruitment Status : Completed
First Posted : July 14, 2011
Results First Posted : April 2, 2015
Last Update Posted : May 14, 2015
|First Submitted Date||July 12, 2011|
|First Posted Date||July 14, 2011|
|Results First Submitted Date||November 28, 2014|
|Results First Posted Date||April 2, 2015|
|Last Update Posted Date||May 14, 2015|
|Start Date||June 2011|
|Primary Completion Date||November 2014 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures
||Incidence of Narcolepsy Among Narcoleptic Subjects Exposed or Unexposed to Vaccine [ Time Frame: Narcolepsy onset during the 16-week post-vaccination period. ]
Incidence rates will be computed by comparing narcolepsy incidence rates in exposed and non-exposed subjects. Comparison of narcolepsy incidence rates in the period prior to vaccine administration and pseudo-vaccine administration will be used to test the comparability of exposed and non-exposed group.
|Original Primary Outcome Measures
||Risk of narcolepsy among vaccinated and non-vaccinated persons, adjusting for age and sex using the Mantel-Haenszel method [ Time Frame: Patients complete a 30-minute questionnaire with the sleep specialist and, if they agree to do the second portion, have a 24-hour investigation in the sleep lab. ]
Risk ratios and attributable risks will be computed by comparing narcolepsy Incidence rates in exposed and non-exposed subjects. Comparison of narcolepsy incidence rates in the period prior to vaccine administration and pseudo-vaccine administration will be used to test the comparability of exposed and non-exposed group.
|Change History||Complete list of historical versions of study NCT01394614 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures||Not Provided|
|Original Secondary Outcome Measures||Not Provided|
|Current Other Outcome Measures||Not Provided|
|Original Other Outcome Measures||Not Provided|
|Brief Title||Risk of Narcolepsy Associated With Administration of H1N1 Vaccine|
|Official Title||Risk of Narcolepsy Associated With Administration of Inactivated Adjuvanted (AS03) A/H1N1 Pandemic Influenza Vaccine in Quebec|
|Brief Summary||The goal of the study is to assess the risk of occurrence of narcolepsy following the administration of inactivated (AS03) adjuvanted A/H1N1 pandemic influenza vaccine in the province of Quebec, Canada, using different case definitions and time intervals to disease onset, while controlling for potential confounding variables such as age, gender, season and, when possible, A/H1N1 pandemic influenza infection. Another aim is to describe the epidemiology and clinical features of narcolepsy cases with onset during the period January 1st, 2009 to December 31, 2010 in the population of Quebec.|
This study aims to describe the epidemiological and clinical characteristics of cases of narcolepsy which occurred in Quebec during the period 1 January 2009 to December 31, 2010 and to assess the risk of developing narcolepsy associated with the vaccine against influenza A/H1N1. The study will last about six months. Based on the prevalence of narcolepsy, an estimated 100 people who developed symptoms of narcolepsy between January 1st, 2009 and December 31, 2010 will participate in this study at the sleep clinic of the Sacré-Coeur Hospital in Montreal.
Narcolepsy is primarily characterized by the presence of excessive daytime sleepiness (EDS) and cataplexy. EDS occurs daily and is usually the most disabling symptom of narcolepsy. Cataplexy consists of a sudden drop of muscle tone triggered by strong and sudden emotions such as laughter, anger and surprise. Cataplexy is the most specific symptom of narcolepsy but it is not present in every patient especially at disease onset. Two other auxiliary symptoms are sleep paralysis and hypnagogic hallucinations either at sleep onset or upon awakening during the night or in the morning. They are present in approximately two thirds of narcoleptic patients especially in the younger individuals during the early stage of narcolepsy. Narcolepsy is associated with an absence or low level of hypocretin1 peptide in the cerebrospinal fluid (CSF).
Narcolepsy with cataplexy can be diagnosed purely on clinical grounds but this diagnosis should whenever possible be confirmed by night-time polysomnography (PSG) followed by the daytime multiple sleep latency test (MSLT). Sleep latency on the MSLT should be inferior or equal to 8 minutes with the presence of two or more sleep onset REM periods (SOREMPs). Human leukocyte antigen (HLA) typing of patients with narcolepsy-cataplexy almost always shows the presence of HLA DQB1*0602. Finally, measuring CSF level of hypocretin-1 is specific and sensitive for the diagnosis of narcolepsy with cataplexy.
Cases of narcolepsy following administration of A/H1N1 pandemic vaccines have been reported in Sweden, Finland, France and Canada. The majority of reports have shown a temporal association with inactivated (AS03) adjuvanted A/H1N1 vaccines. These cases had some common features: severe sleepiness and presence of cataplexy, abrupt onset and rapid evolution, presence of HLA DBQ1*0602 marker, very low CSF hypocretin-1, and positive MSLT test. At the request of the European Medicines Agency (EMA), a series of investigations have been considered by GlaxoSmithKline Biologicals, including one in Quebec. In this province, following the report of four cases of narcolepsy with cataplexy potentially associated with administration of Arepanrix, our research team was contacted both by federal and provincial public health authorities to evaluate the possibility of an independent investigation.
A retrospective cohort study is proposed. The existence of a comprehensive influenza immunization registry in Quebec allows a precise identification of the cohort of exposed subjects, by age and gender. Exposed subjects will be followed from the time of vaccine administration (first dose of inactivated AS03 A/H1N1 pandemic vaccine) as recorded in the immunization registry. The size of non-exposed subjects by gender- and age-specific categories will be estimated from the number in census data (a more accurate source than provincial health insurance data) minus the number in the influenza immunization registry. Pseudo-dates of vaccine administration will be generated for non-exposed subjects based on the distribution of dates of vaccinated subjects. Non-exposed subjects will be followed from the pseudo-date of vaccine administration.
All neurologists, pulmonologists, neuro-pediatricians and child psychiatrists practicing in the province of Quebec will be contacted and asked to report confirmed or suspected cases of narcolepsy with onset during the period from January1st, 2009 to December 31, 2010. Patients will be contacted by their physicians and invited to call the sleep center to participate in a study of newly diagnosed cases of narcolepsy. They will then undergo a brief screening telephone questionnaire. At this point, if they meet the minimum criteria of narcolepsy, they will be asked if they agree to participate in the study. The study includes, at first, signing a consent form and completing a questionnaire.
The questionnaire includes questions on demographics, medical history, medications, and detailed questions about symptoms of narcolepsy. In children, the information will be based on parental responses. A physician specializing in sleep medicine will call the participant to review the questionnaire with him and will propose a series of tests at the sleep laboratory of the 'Hôpital du Sacré-Coeur de Montréal', including nocturnal polysomnography, MSLT test, blood sampling (for HLA typing) and, lumbar puncture (for hypocretin measurements). Patients will sign a second consent form on site at 'Hôpital du Sacré-Coeur de Montréal' if they agree to participate in that second portion of the study. Monitoring of subjects during the study will be done under the supervision of Dr. Jacques Montplaisir, MD, PhD.
|Study Design||Observational Model: Cohort
Time Perspective: Retrospective
|Target Follow-Up Duration||Not Provided|
|Biospecimen||Retention: Samples With DNA
|Sampling Method||Non-Probability Sample|
|Study Population||The study population includes persons more than 6 months of age residing in the province of Quebec.|
|Intervention||Biological: A/H1N1 vaccine
Verify if exposure to Arepanrix vaccine increase risk of developing narcolepsy in 16 weeks post-vaccination.
Other Name: Arepanrix vaccine
|Publications *||Montplaisir J, Petit D, Quinn MJ, Ouakki M, Deceuninck G, Desautels A, Mignot E, De Wals P. Risk of narcolepsy associated with inactivated adjuvanted (AS03) A/H1N1 (2009) pandemic influenza vaccine in Quebec. PLoS One. 2014 Sep 29;9(9):e108489. doi: 10.1371/journal.pone.0108489. eCollection 2014.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Completion Date||November 2014|
|Primary Completion Date||November 2014 (Final data collection date for primary outcome measure)|
|Ages||6 Months and older (Child, Adult, Senior)|
|Accepts Healthy Volunteers||No|
|Contacts||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries||Canada|
|Removed Location Countries|
|Other Study ID Numbers||Narco-H1N1|
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Jacques Montplaisir, Hopital du Sacre-Coeur de Montreal|
|Study Sponsor||Hopital du Sacre-Coeur de Montreal|
|PRS Account||Hopital du Sacre-Coeur de Montreal|
|Verification Date||May 2015|