RecruitingNCT05878730

Melatonin and Response to Lithium

A Case-control Study Comparing Melatonin Nocturnal Secretion Between Lithium Responders Versus Non Responders in Type 1 Bipolar Disorder.


Sponsor

Assistance Publique - Hôpitaux de Paris

Enrollment

60 participants

Start Date

Jul 26, 2023

Study Type

OBSERVATIONAL

Conditions

Summary

Bipolar disorders are mental illnesses characterized by the recurrence of mood-episodes, that can have a severe impact on the life of individuals. The effect of lithium, one of the main medications used to treat acute episodes or prevent them from happening, is very different from one individual to an-other. So far, there is no way to predict in advance for whom patient this treatment will be effective or for whom it will not. Finding markers that can predict as early as possible the efficiency of this treatment is a major field of current research in psychiatry, in order to avoid maintaining an inefficient treatment for several years that can have negative side-effects. Over the past decades, it has been shown by multiple studies that lithium can act on the biological clock, that regulates circadian rhythmicity of the body (i.e. rhythms that presents a 24 hours periods, such as rhythms of sleep and activity, feeding, social activities...). But it is still very unclear whether the effect of lithium in regulating the mood in bipolar disorders is mediated by this action. Melatonin is one of the key-regulator of circadian rhythmicity of the human body. Our hypothesis, based on some previous studies, is that the action of lithium in type-1 bipolar disorder (BD-I) is related to an action on melatonin secretion. To test that, we want in this study to compare the noctunal secretion of melatonin between BD-I individuals with a good response to lithium versus with a poor response to lithium.


Eligibility

Min Age: 18 YearsMax Age: 70 Years

Inclusion Criteria7

  • BD-1 as defined by DSM-5
  • Age : 18 to 70
  • Current treatment by lithium for more than one year
  • Euthymia defined by : MADRS <8 and YMRS <8 at inclusion ; no hospitalization or change in mood-stabilizing treatment in the previous 3 months
  • Health condition compatible with blood and urinal sampling
  • Being affiliated to french social security
  • Written consent

Exclusion Criteria9

  • Treatment by : melatonin, agomelatin, benzodiazepines or hypnotic in the last 15 days
  • Treatment by a strong CYP1A2 inducer in the last month : ciprofloxacine, dihydralazine, fluvoxamine, norfloxacine
  • Current substance use disorder except for tobacco
  • Chronic renal failure with glomerular filtration rate <60mL/min
  • Jetlag in the last 15 days or life-event impacting circadian rhythmicity (birth, grief, night-work...)
  • Sleep disorders such as Obstructive Sleep-Apnea, restless leg syndrome, narcolepsy
  • Pregnancy, breastfeeding
  • Guardianship
  • Inability to understand french, illiteracy

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Interventions

DIAGNOSTIC_TESTurine collection

* Urine collection will be made on a 12 hours period (20h00-8h00), the night before V2 * at V2 : 2 mL urinal sample for measure of 6-SMT concentration (ng/mL) and creatinin (mg/mL) * Measure of 6-SMT will be made by a validated radio-immunology assay

DIAGNOSTIC_TESTLevel of Proteins

* blood sample at V2 (2x3.5mL citrate tubes) * measured by ELISA

DIAGNOSTIC_TESTLevel of mRNA and miRNA

* blood sample at V2 (2x2.5mL PAX-gene tube) * measured by quantitative RT-PCR

DIAGNOSTIC_TESTLevel of plasmatic and intraerythrocytic lithium

* blood sample at V2 (mmol/L) * 4mL EDTA tube


Locations(1)

Hôpital Fernand-Widal

Paris, Île-de-France Region, France

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NCT05878730


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