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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Anticipated)

320

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Paris, France, 75010
        • Hopital Fernand Widal

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 68 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

individuals with bipolar I disorder

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
bipolar I disorders who initiate 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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

month 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Month 24
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.
Month 24
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
Month 24
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
Month 24
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
Month 24
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
Month 24
Monthly qIDS
Time Frame: monthly from month 1 to month 24
Quick Inventory of Depressive Symptoms (qIDS)
monthly from month 1 to month 24
Monthly BRMS
Time Frame: monthly from month 1 to month 24
Bech Rafaelson Mania Scale (BRMS)
monthly from month 1 to month 24
Monthly BPRS
Time Frame: monthly from month 1 to month 24
Brief Psychosis Rating Scale (BPRS)
monthly from month 1 to month 24
Monthly ISS
Time Frame: monthly from month 1 to month 24
Internal State Scale (ISS)
monthly from month 1 to month 24
Monthly LIFE-II
Time Frame: monthly from month 1 to month 24
Longitudinal Interval Follow-up Evaluation (LIFE-II)
monthly from month 1 to month 24
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)
Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 21, month 24
Cost-effectiveness
Time Frame: Month 24
EuroQOL-5D scale
Month 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 10, 2020

Primary Completion (Anticipated)

June 1, 2024

Study Completion (Anticipated)

June 1, 2024

Study Registration Dates

First Submitted

December 20, 2019

First Submitted That Met QC Criteria

December 20, 2019

First Posted (Actual)

December 23, 2019

Study Record Updates

Last Update Posted (Actual)

July 13, 2022

Last Update Submitted That Met QC Criteria

July 12, 2022

Last Verified

July 1, 2022

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Bipolar I Disorder

Clinical Trials on lithium treatment

3
Subscribe