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Optimizing Response to Li Treatment Through Personalized Evaluation of Individuals With Bipolar I Disorder: The R-LiNK Initiative (R-LiNK)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04209140
Recruitment Status : Not yet recruiting
First Posted : December 23, 2019
Last Update Posted : December 23, 2019
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:

Bipolar disorder (BD), especially BD type I, is a highly prevalent mental disorder and a is a highly prevalent mental disorder and an important factor for suicide. Lithium is the key treatment for prevention of BD relapse and has a proven suicide prevention effect. Whilst many cases become asymptomatic with lithium treatment, the majority show sub-optimal response.

The objectives of this project are to:

  • improve outcomes of bipolar I disorder (BDI) cases prescribed lithium through the application of stratified approaches
  • optimize the early prediction of lithium response using a set of multi-modal biomarkers ("blood omics", Magnetic Resonance Imaging and Li7-Magnetic Resonance Spectroscopy derived-markers)
  • develop a multidisciplinary multinational network of experts to undertake this and future projects on personalized diagnostics and therapeutics and
  • implement new, powerful technologies to characterize brain lithium distribution and the blood molecular signature of lithium in responders and non-responders.

This cutting edge approach will identify the eligibility criteria for treatment with lithium in BD in terms of response, safety and tolerability.


Condition or disease Intervention/treatment
Bipolar I Disorder Drug: lithium treatment

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Study Type : Observational
Estimated Enrollment : 320 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Optimizing Response to Li Treatment Through Personalized Evaluation of Individuals With Bipolar I Disorder: The R-LiNK Initiative
Estimated Study Start Date : January 2020
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : January 2024

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
bipolar I disorders who initiate lithium treatment Drug: lithium treatment

Decisions relating to treatment are also considered the clinician's responsibility to be made according to bipolar treatment guidelines and international standards of care (e.g. discontinuation, co-prescriptions, and according to SmPC in force). After the clinician has confirmed the indication of Lithium treatment as well as the absence of contra-indicated concomintant medication (NSAIDs and Diuretics) and after pre-

Lithium evaluations confirm the absence of contra-indication, Lithium is initiated following standard of care:

progressive titration to reach therapeutic plasma levels. Clinicians will use the therapeutic range provided by the laboratory they use in their usual clinical practice and according to the type of Lithium they prescribe.





Primary Outcome Measures :
  1. Responder [ Time Frame: month 24 ]

    Good Responder The individual meets criteria for sustained remission, namely they experience euthymia (defined as a score on the Quick Inventory of Depressive Symptoms (qIDS)<6 and the Bech Rafaelson Mania Scale (BRMS)<7) for at least 8 weeks during the two-year follow-up period without evidence of relapse into a syndromal episode of BD at any time after achieving sustained euthymia. AND No addition of a new mood stabilizer with the purpose of promoting mood stabilisation after lithium initiation

    Non Responder

    The individual:

    Fails to meet criteria for sustained remission (euthymia defined as a score on the qIDS<6 and the BRMS<7 for a minimum period >=8 consecutive weeks) during the two-year follow-up.

    OR Experiences >=1 relapse into a syndromal episode of BD of any polarity during the two-year follow-up period without any period of sustained remission

    Definition of a Partial Responder All cases not fulfilling the criteria of Good Responders or Non Responders



Secondary Outcome Measures :
  1. Adherence [ Time Frame: Month 24 ]
    Adequate adherence will be defined as the individual taking at least 70% of the Li prescribed (i.e. either >70% prescribed dose &/or >70% of the time) based on the monthly assessment of adherence

  2. Alda Scale [ Time Frame: Month 24 ]
    Alda scale defined in the following article : Grof P, Duffy A, Cavazzoni P, Grof E et al. Is response to prophylactic lithium a familial trait? J Clin Psychiatry. 2002 Oct;63(10):942-7.

  3. Responder - sensitivity [ Time Frame: Month 24 ]
    Good Responders= Recorded improvement of illness activity is >=70% AND no addition of mood stab after Li initiation Non Responders= Recorded improvement of illness activity is <=30% whatever the treatment has been Partial Responders = Recorded improvement of illness activity is between 70 and 30% whatever the treatment has been OR Recorded improvement of illness activity is >=70% but the addition of mood stab after Li initiation has occurred

  4. Time to new BD [ Time Frame: Month 24 ]
    Time to a new Bipolar Disorder (BD) episode, defined as the delay between inclusion and the date of the diagnosis of new Bipolar disorder

  5. Time to BD hospitalization [ Time Frame: Month 24 ]
    Time to a new hospitalization for BD, defined as the delay between inclusion and the date of new hospitalization for Bipolar disorder

  6. Time to new mood stabilizer [ Time Frame: Month 24 ]
    Time to prescription of a new mood stabilizer, defined as the delay between inclusion and the date of prescription of a new mood stabilizer

  7. Monthly qIDS [ Time Frame: monthly from month 1 to month 24 ]
    Quick Inventory of Depressive Symptoms (qIDS)

  8. Monthly BRMS [ Time Frame: monthly from month 1 to month 24 ]
    Bech Rafaelson Mania Scale (BRMS)

  9. Monthly BPRS [ Time Frame: monthly from month 1 to month 24 ]
    Brief Psychosis Rating Scale (BPRS)

  10. Monthly ISS [ Time Frame: monthly from month 1 to month 24 ]
    Internal State Scale (ISS)

  11. Monthly LIFE-II [ Time Frame: monthly from month 1 to month 24 ]
    Longitudinal Interval Follow-up Evaluation (LIFE-II)

  12. WHODAS [ Time Frame: Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 21, month 24 ]
    World Health Organisation Disability Assessment Scale (WHODAS)

  13. Cost-effectiveness [ Time Frame: Month 24 ]
    EuroQOL-5D scale



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
individuals with bipolar I disorder
Criteria

Inclusion Criteria:

  • Decision to prescribe Li as a prophylactic treatment based on clinicians' assessment
  • Confirmed diagnosis of BD1 according to DSM-5 criteria
  • Aged 18-70 years.
  • Able and willing to give written informed consent
  • consents to blood sample for the purpose of the RLiNK study
  • Covered by a Social Security Insurance where applicable
  • Patients on Curatorship (consent form signed by the patient and specific consent form for the curator)

Exclusion Criteria:

  • Trial of Lithium undertaken within the last 6 months
  • Lifetime history of mood disorder better explained by a DSM-5 definition for schizoaffective disorder
  • 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/1.73m 2
  • On-going Pregnancy or planned pregnancy on the next 2 years
  • Lactating and breast feeding women (see SmPc)
  • Pregnant women

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04209140


Contacts
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Contact: franck BELLIVIER, MD PhD 140054225 ext +33 frank.bellivier@inserm.fr
Contact: Matthieu RESCHE-RIGON, MD PhD 142499742 ext +33 matthieu.resche-rigon@u-paris.fr

Locations
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France
Hôpital Fernand Widal
Paris, France, 75010
Contact: Bruno ETAIN, MD PHD    140054225 ext +33    bruno.etain@aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT04209140    
Other Study ID Numbers: P180101
2018-002263-26 ( EudraCT Number )
First Posted: December 23, 2019    Key Record Dates
Last Update Posted: December 23, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Disease
Pathologic Processes
Lithium Carbonate
Antidepressive Agents
Psychotropic Drugs
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs