Bipolar Disorder IMeLiRNCT05878730
Melatonin and Response to Lithium
An observational study of Bipolar Disorder I, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Bipolar Disorder I
- What is being tested?
- urine collection, Level of Proteins and Level of mRNA and miRNA
- How many people
- 60 participants
- Where
- 1 siteFrance
- Study dates
- 26 Jul 2023to Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Adult, Older adult
Study population: Euthymic BD-1 patients treated by lithium
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- Pregnancy, breastfeeding
- Guardianship
- Inability to understand french, illiteracy
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Hôpital Fernand-Widal
Paris, Île-de-France Region, 75010
Vincent Hennion, MD, 01 40 05 42 08 ext. +33, vincent.hennion@aphp.fr
About this study
Official title: A Case-control Study Comparing Melatonin Nocturnal Secretion Between Lithium Responders Versus Non Responders in Type 1 Bipolar Disorder.
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.
Read more
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.
Read the detailed description
The study is a monocentric case-control study comparing the level of urinary nocturnal secretion of 6-sulfatoxy-melatonin between good-responders (GR) and non-responders (NR) to lithium in euthymic BD-1 individuals.
The study will also compare the levels of 14-3-3 proteins and miR-451 between these two groups. They are regulators of melatonin-synthesis, that on one hand have been previously associated in autism spectrum disorders to melatonin level modifications and on the other hand have been shown in one preclinical study in rat to be regulated by a lithium treatment.The study also compare the levels of other proteins and mRNA of interest related to ciracdian regulatory pathways.
Euthymic BD-1 patients treated by lithium will be pre-selected and lithium response will be assessed by clinicians using the validated ALDA-scale.
V1 = inclusion (D0) :
- assessment of inclusion and exclusion criteria
- written consent
- collection of socio-demographic data, clinical data
- questionaries : MADRS (Montgomery-Absberg Depressive scale for depressive symptoms), YMRS (Young Mania Rating Scale for manic symptoms), Berlin score (risk of undiagnosed obstructive sleep apnea)
- ALDA scale for assessment of lithium response
- information and furniture for one-night urine collection and one-week sleep diary
- planning of V2, the day after diurnal urine collection
V2 (D8 to D30):
- collection of the urine collection and the sleep diary
- blood sample for measure of plasmatic level of lithium, 14.3.3 proteins and miR-451, mRNA or proteins of interest
- Self-questionaries : PSQI (Pittsburg Sleep Quality Index for sleep assesment), CSM (Composite Scale of Morningness for assessment of morning vs evening chronotype), CTI (Circadian Type Inventory for assessment of chronotype)
- Conditions
- Bipolar Disorder I
- Being tested
- urine collection, Level of Proteins, Level of mRNA and miRNA, Level of plasmatic and intraerythrocytic lithium
- Keywords
- lithium
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
urine collectionDiagnostic 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 ProteinsDiagnostic test
- blood sample at V2 (2x3.5mL citrate tubes)
- measured by ELISA
Level of mRNA and miRNADiagnostic test
- blood sample at V2 (2x2.5mL PAX-gene tube)
- measured by quantitative RT-PCR
Level of plasmatic and intraerythrocytic lithiumDiagnostic test
- blood sample at V2 (mmol/L)
- 4mL EDTA tube
| Study group | Role | What they receive |
|---|---|---|
| good-responders (GR) to lithium in euthymic BD-1 individuals | Not described Receives: Diagnostic Test: urine collection; Diagnostic Test: Level of Proteins; Diagnostic Test: Level of mRNA and miRNA; Diagnostic Test: Level of plasmatic and intraerythrocytic lithium | |
| non-responders (NR) to lithium in euthymic BD-1 individuals | Not described Receives: Diagnostic Test: urine collection; Diagnostic Test: Level of Proteins; Diagnostic Test: Level of mRNA and miRNA; Diagnostic Test: Level of plasmatic and intraerythrocytic lithium |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: at day 30
Secondary outcomes (3)
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
Measured: at day 30
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
Measured: at day 30
Level of plasmatic and intraerythrocytic lithium
Level of plasmatic and intraerythrocytic lithium (mmol/L)
- blood sample at D30 (mmol/L)
- 4mL EDTA tube
Measured: at day 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2023
- Study start26 Jul 2023
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bipolar Disorder IStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05878730
- Sponsor's protocol ID
- APHP221168
- Other IDs
- 2022-A02550-43
- Acronym
- MeLiR
- Status last verified
- Aug 2026
- First submitted
- 19 May 2023
- Last updated
- 18 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Case-control Study Comparing Melatonin Nocturnal Secretion Between Lithium Responders Versus Non Responders in Type 1 Bipolar Disorder.
- ClinicalTrials.gov ID
- NCT05878730
- Acronym / sponsor ID
- MeLiR / APHP221168
- Conditions
- Bipolar Disorder I
- Keywords
- lithium
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 26 Jul 2023 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 26 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The study is a monocentric case-control study comparing the level of urinary nocturnal secretion of 6-sulfatoxy-melatonin between good-responders (GR) and non-responders (NR) to lithium in euthymic BD-1 individuals.
The study will also compare the levels of 14-3-3 proteins and miR-451 between these two groups. They are regulators of melatonin-synthesis, that on one hand have been previously associated in autism spectrum disorders to melatonin level modifications and on the other hand have been shown in one preclinical study in rat to be regulated by a lithium treatment.The study also compare the levels of other proteins and mRNA of interest related to ciracdian regulatory pathways.
Euthymic BD-1 patients treated by lithium will be pre-selected and lithium response will be assessed by clinicians using the validated ALDA-scale.
V1 = inclusion (D0) :
- assessment of inclusion and exclusion criteria
- written consent
- collection of socio-demographic data, clinical data
- questionaries : MADRS (Montgomery-Absberg Depressive scale for depressive symptoms), YMRS (Young Mania Rating Scale for manic symptoms), Berlin score (risk of undiagnosed obstructive sleep apnea)
- ALDA scale for assessment of lithium response
- information and furniture for one-night urine collection and one-week sleep diary
- planning of V2, the day after diurnal urine collection
V2 (D8 to D30):
- collection of the urine collection and the sleep diary
- blood sample for measure of plasmatic level of lithium, 14.3.3 proteins and miR-451, mRNA or proteins of interest
- Self-questionaries : PSQI (Pittsburg Sleep Quality Index for sleep assesment), CSM (Composite Scale of Morningness for assessment of morning vs evening chronotype), CTI (Circadian Type Inventory for assessment of chronotype)
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| good-responders (GR) to lithium in euthymic BD-1 individuals | – | Diagnostic Test: urine collection, Diagnostic Test: Level of Proteins, Diagnostic Test: Level of mRNA and miRNA, Diagnostic Test: Level of plasmatic and intraerythrocytic lithium |
| non-responders (NR) to lithium in euthymic BD-1 individuals | – | Diagnostic Test: urine collection, Diagnostic Test: Level of Proteins, Diagnostic Test: Level of mRNA and miRNA, Diagnostic Test: Level of plasmatic and intraerythrocytic lithium |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Euthymic BD-1 patients treated by lithium
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (9 listed)
- 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...)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| urine 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 test | good-responders (GR) to lithium in euthymic BD-1 individuals, non-responders (NR) to lithium in euthymic BD-1 individuals |
| Level of Proteins* blood sample at V2 (2x3.5mL citrate tubes) * measured by ELISA | Diagnostic test | good-responders (GR) to lithium in euthymic BD-1 individuals, non-responders (NR) to lithium in euthymic BD-1 individuals |
| Level of mRNA and miRNA* blood sample at V2 (2x2.5mL PAX-gene tube) * measured by quantitative RT-PCR | Diagnostic test | good-responders (GR) to lithium in euthymic BD-1 individuals, non-responders (NR) to lithium in euthymic BD-1 individuals |
| Level of plasmatic and intraerythrocytic lithium* blood sample at V2 (mmol/L) * 4mL EDTA tube | Diagnostic test | good-responders (GR) to lithium in euthymic BD-1 individuals, non-responders (NR) to lithium in euthymic BD-1 individuals |
Primary outcome
Ratio between 6-sulfatoxy-melatonin (6-SMT) concentration and creatinin concentration on a 12-hours nocturnal urine collection
Time frame: at day 30
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
3 secondary outcomes
Level of Proteins
Time frame: at day 30
Level of mRNA and miRNA
Time frame: at day 30
Level of plasmatic and intraerythrocytic lithium
Time frame: at day 30
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2026.
- Individual participant dataSharing planned: No
Related trials for Bipolar Disorder I
RecruitingPhase 3
A Study to Assess the Long-term Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder (BALSAM-3)
Bipolar Disorder Type I With Mania
RecruitingPhase 2
NMDA Receptor Modulation for the Treatment of Bipolar I Disorder
Bipolar I Disorder
RecruitingPhase 3
A Study to Evaluate the Efficacy and Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder
Bipolar-I Disorder With Mania or Mania With Mixed Features
RecruitingPhase 3
A Study to Evaluate the Efficacy and Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder (BALSAM-2)
Bipolar Disorder Type I With Mania or Mania With Mixed Features
Enrolling by invitationObservational study
Digital Phenotypes for Predicting Depression_Validation
Major Depressive Disorder, Bipolar I Disorder
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Bipolar Disorder I, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Vincent Hennion, MD (01 40 05 42 08 ext. +33, vincent.hennion@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ratio between 6-sulfatoxy-melatonin (6-SMT) concentration and creatinin concentration on a 12-hours nocturnal urine collection (time frame: at day 30). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2026.