Clinical trial NCT02627404: Study of the Genetic and Environmental Factors of Vulnerability in Bipolar Disorders
Official title: Study of the Genetic and Environmental Factors of Vulnerability in Bipolar Disorders
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Bipolar Disorder
Keywords: Bipolar disorders
Genetic
Biomarkers
Circadian rhythm
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2015-12-10
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Bipolar disorder is a complex, multifactorial disorder with the intervention of genetic vulnerability factors. To help the identification of these genetic factors and to improve genotype-phenotype correlation, the identification of endophenotype through the exploration of vulnerability characteristics in unaffected first degree relatives have been recommended. For this purpose, the investigator include bipolar patients, unaffected first degree relatives and control subjects to perform genetic association studies and subphenotype analyses. In this study the investigator will focus on subgroups defined according to the existence of abnormal circadian rhythm (a major indicator of bipolar vulnerability).

Lithium is the leading treatment of bipolar disorders but prophylactic lithium response is highly variable and difficult to predict due to lack of biomarkers of response. To explore lithium response variability and to identify biomarkers of response, the investigator characterise lithium response using "ALDA" scale to conduct pharmacogenetic studies and pharmacokinetic studies of lithium extended release, in the subpopulation of patients treated with lithium. As lithium is a circadian agent, the investigator will also explore the links between lithium response and circadian phenotypes. Finally, using Li7 magnetic spectroscopy, the investigator will compare lithium brain distribution in a small sample of good and partial responders to lithium.


Eligibility criteria: Inclusion Criteria:

* Patients with Bipolar I, II or Not Otherwise Specified (NOS) disorders
* Euthymic
* Age \> 18
* Affiliated to the French social health care system
* Somatic state compatible with a blood test
* Informed consent signed for the study
* European

Exclusion Criteria:

* Patients major protected
* Patients adopted
* Geographical origin of grandparents unknown

Primary outcomes:
measure: Allele frequencies
timeFrame: All genotyping will be performed after 6 years
Secondary outcomes:
measure: Mean Activity (movement per minute)
timeFrame: End of participation of the activity tracking module : Day 21
measure: Total time in bed (minutes)
timeFrame: End of participation of the activity tracking module : Day 21
measure: Total time in bed with and without sleep (minutes)
timeFrame: End of participation of the activity tracking module : Day 21
measure: Day to day Stability in Time to bed (ratio of minutes)
timeFrame: End of participation of the activity tracking module : Day 21
measure: Day to day Stability in activity (ratio of minutes)
timeFrame: End of participation of the activity tracking module : Day 21
measure: Sleep latency (minutes)
timeFrame: End of participation of the activity tracking module : Day 21
measure: Total time awaken during the night (minutes)
timeFrame: End of participation of the activity tracking module : Day 21
measure: Time awaken during the night (minutes)
timeFrame: End of participation of the activity tracking module : Day 21
measure: Percentage of time sleeping (%)
timeFrame: End of participation of the activity tracking module : Day 21
measure: Fragmentation index (ratio)
timeFrame: End of participation of the activity tracking module : Day 21
measure: Total sleep time (minutes)
timeFrame: End of participation of the activity tracking module : Day 21
measure: Activity during sleep (movement per minute)
timeFrame: End of participation of the activity tracking module : Day 21
measure: Total activity amplitude (movement per minute)
timeFrame: End of participation of the activity tracking module : Day 21
measure: Start L5: start of the 5 hours with the lowest activity period (hours:minutes)
timeFrame: End of participation of the activity tracking module : Day 21
measure: Start M10: start of the 10 hours with the highest activity period (hours:minutes)
timeFrame: End of participation of the activity tracking module : Day 21
measure: Plasma and erythrocyte lithium concentration (Meq/L) at different times after inclusion
timeFrame: At inclusion : time 0, 1 hour, 4 hours and 8 hours - At Day 30 : Time 0 and 1 hour
measure: Lithium brain distribution using Li7 magnetic spectroscopy
timeFrame: Day 1
Other outcomes:
Locations:
city: Paris
country: France
Study officials:
References:
citation: Loftus J, Scott J, Vorspan F, Icick R, Henry C, Gard S, Kahn JP, Leboyer M, Bellivier F, Etain B. Psychiatric comorbidities in bipolar disorders: An examination of the prevalence and chronology of onset according to sex and bipolar subtype. J Affect Disord. 2020 Apr 15;267:258-263. doi: 10.1016/j.jad.2020.02.035. Epub 2020 Feb 19.
citation: Geoffroy PA, Micoulaud Franchi JA, Maruani J, Philip P, Boudebesse C, Benizri C, Yeim S, Benard V, Brochard H, Leboyer M, Bellivier F, Etain B. Clinical characteristics of obstructive sleep apnea in bipolar disorders. J Affect Disord. 2019 Feb 15;245:1-7. doi: 10.1016/j.jad.2018.10.096. Epub 2018 Oct 9.
citation: Richard-Lepouriel H, Kung AL, Hasler R, Bellivier F, Prada P, Gard S, Ardu S, Kahn JP, Dayer A, Henry C, Aubry JM, Leboyer M, Perroud N, Etain B. Impulsivity and its association with childhood trauma experiences across bipolar disorder, attention deficit hyperactivity disorder and borderline personality disorder. J Affect Disord. 2019 Feb 1;244:33-41. doi: 10.1016/j.jad.2018.07.060. Epub 2018 Aug 6.