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Melatonin and Response to Lithium

ConditionBipolar Disorder I
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18-70
SponsorAssistance Publique - Hôpitaux de Paris

About this trial

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 criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial population

Euthymic BD-1 patients treated by lithium

Trial design

Design model

Case-control

Time perspective

Prospective

Treatments tested in this trial

  • urine collection

    Diagnostic test

    * 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

  • Level of Proteins

    Diagnostic test

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

  • Level of mRNA and miRNA

    Diagnostic test

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

  • Level of plasmatic and intraerythrocytic lithium

    Diagnostic test

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

Treatment groups

60 Participants
are divided into 2 treatment groups
Group A: good-responders (GR) to lithium in euthymic BD-1 individuals4 interventions
Group B: non-responders (NR) to lithium in euthymic BD-1 individuals4 interventions

Trial outcomes

Primary outcomes

1

Ratio between 6-sulfatoxy-melatonin (6-SMT) concentration and creatinin concentration on a 12-hours nocturnal urine collection

Ratio between 6-sulfatoxy-melatonin (6-SMT) concentration and creatinin concentration on a 12-hours nocturnal urine collection (8pm to 8am) : * Urine collection will be made on a 12 hours period (20h00-8h00), the night before D30 * at D30 : 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

Time frame
at day 30

Secondary outcomes

1

Level of Proteins

Level of Proteins (including protein 14.3.3) in ng/mL : * blood sample at D30 (2x3.5mL citrate tubes) * measured by ELISA

Time frame
at day 30
2

Level of mRNA and miRNA

Level of mRNA and miRNA (including miR-451) * blood sample at D30 (2x2.5mL PAX-gene tube) * measured by quantitative RT-PCR

Time frame
at day 30
3

Level of plasmatic and intraerythrocytic lithium

Level of plasmatic and intraerythrocytic lithium (mmol/L) * blood sample at D30 (mmol/L) * 4mL EDTA tube

Time frame
at day 30

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Assistance Publique - Hôpitaux de Paris

Lead sponsor

Source ClinicalTrials.gov
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