E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult individuals with bipolar I disorders who initiate lithium treatment based on the decision of themselves and their clinician |
Voksne individer med bipolar type-1 lidelse, der initierer lithiumbehandling baseret på selv og deres klinikeres beslutning
|
|
E.1.1.1 | Medical condition in easily understood language |
Adult individuals with bipolar I disorders who initiate lithium treatment based on the decision of themselves and their clinician |
Voksne individer med bipolar type-1 lidelse, der initierer lithiumbehandling baseret på selv og deres klinikeres beslutning |
|
E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10057667 |
E.1.2 | Term | Bipolar disorder |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective of this study is to identify the eligibility criteria for treatment with Li in BDI in terms of response, safety and tolerability Primary Objective: To evaluate the predictive values of the biomarkers collected during the first three months of Lithium treatment on long term Lithium response (2 years) define according the primary outcome measures |
Formålet med denne undersøgelse er at identificere udvælgelseskriterierne for behandling med Li i BDI med hensyn til respons, sikkerhed og tolerabilitet. Primærmål: At evaluere de prædikative værdier af biomarkørerne, der er indsamlet i løbet af de første tre måneder af lithiumbehandling, på lithium respons på lang sigt (2 år) defineret i henhold til det primære effektmål |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the prognostic values of the biomarkers collected during the first three months of Lithium treatment on long term Lithium response (2 years) define according the secondary outcome measures |
For at evaluere de prognostiske værdier af biomarkørerne, der er indsamlet i løbet af de første tre måneder af lithiumbehandling, på lithium respons på lang sigt (2 år) defineret i henhold til de sekundære effektmål. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Decision to prescribe Li as a prophylactic treatment based on clinicians' assessment 2. Confirmed diagnosis of BD1 according to DSM-5 criteria [based on the Mood section of the SCID] 3. Aged 18-70 years. 4. Able and willing to give written informed consent 5. Eligible for, and consents to blood sample for the purpose of the RLiNK study 6. Covered by a Social Security Insurance where applicable |
|
E.4 | Principal exclusion criteria |
1 Trial of Lithium undertaken within the last 6 months 2 Lifetime history of mood disorder better explained by a DSM-5 definition for schizoaffective disorder [based on the relevant section of the SCID] 3 Pre-lithium screening suggest that Lithium initiation is contraindicated: - Incompatible concurrent treatments: long-term use of non-steroidal anti-inflammatory drug or diuretics for a known and established comorbid disorder with no possible alternative treatment (i.e. absolute contra-indication to Li treatment) - Health issues (risk of worsening of a pre-existing condition) Psoriasis, Brugada syndrome - Renal dysfunction: Glomerular Filtration rate below 60mL/min/1.73m2 - On-going Pregnancy or planned pregnancy on the next 2 years - Lactating and breast feeding women (see SmPc) - pregnant women
- All contra-indications mentionned in the SmPC Lithium of the country
Woman of childbearing potential, defined as not meeting at least one of the following criteria, are required to undergo a pregnancy test at least at the beginning and the end of the study: • Post-menopausal (no menses for 12 months without an alternative medical cause or FSH greater than 40 U/ml for 6 months) • Sterilization (hysterectomy, bilateral salpingectomy, bilateral tubal occlusion or bilateral oophorectomy) • Consistent and correct application of contraceptives with a failure less than 1% per year (defined as highly effective birth control method). Contraception should be used for a minimum of 4 days (5 half-lives) after last treatment dose Such methods include: o combined (estrogen an progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal) o progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable) o intrauterine device (IUD) o intrauterine hormone-releasing system (IUS) o sexual abstinence o vasectomy of the partner 4 Participation in another research protocol that interferes with the evaluation of Lithium response (efficacy or tolerance) 5 Severe risk of self-harm at present, based on clinician’s evaluation 6 Patients on Tutorship (France) Protected adult without current capacity to consent (other countries) 7 Persons under the protection of justice
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
After all study participants have completed the follow-up period, the expert panel will reach a consensus on the classification of each participant into one of three categories: (i) good responders (GR), (ii) partial responders (PR), (iii) non-responders (NR). If no clinical followup data are available, the participant will be categorized as unclassifiable (UC). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
After all study participants have completed the follow-up period, the expert panel will reach a consensus on the classification of each participant into one of three categories: (i) good responders (GR), (ii) partial responders (PR), (iii) non-responders (NR). If no clinical followup data are available, the participant will be categorized as unclassifiable (UC). |
|
E.5.2 | Secondary end point(s) |
There are several possible definitions of treatment response that employ different levels of precision. a) Response assessed retrospectively by estimating the total score b) Time dependent measures of outcome c) Continuous ratings of BD symptoms |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
The durations of the clinician-rated and self-questionnaires at each visit are detailed in Table 3 of the protocole - Definition of a Missing face to face visit: Planned appointment + 1month - Definition of a Missing telephone visit: Planned appointment + 1 week - In case of missing visit the information needed to inform the primary outcome (such as relapse, hospitalisation, suicide attempt, comorbidities…) will be collected retrospectively at the next visit. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Prospective clinical multi centre cohort study |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Denmark |
France |
Germany |
Italy |
Norway |
Spain |
Sweden |
United Kingdom |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Participants may exit the study at any time and for any reason. The clinician and the investigator can decide the discontinuation based on the withdrawal of the consent, the compliance to the study (missing visits) and safety issues. In case of consent withdrawal, the data already collected will be used for the analyses unless the participant asks for the destruction of these data. These participants will remain in the study (intent to treat analyses) and will be analysed. |
Deltagere kan forlade studiet til enhver tid og af enhver grund. Klinikeren og efterforskeren kan vælge at afbryde forsøget for en deltager baseret på tilbagekaldelse af samtykke, manglende overholdelse af undersøgelsen (manglende besøg) og ved sikkerhedsproblemer. Ved tilbagekaldelse af samtykke vil de data, der allerede er indsamlet, blive brugt til analyser, medmindre deltageren beder om at disse data bliver destrueret. Disse deltagere vil dog forblive i undersøgelsen mhp. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 36 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 36 |