The R-LiNK project

Consortium Members

R-LiNK Partners

France

INSERM - Frank Bellivier / Cynthia Marie Claire

Research Unit INSERM UMR_S 1144 “ Response Variability to Psychotropics “(Director: Jean-Louis Laplanche, PharmD, PhD,).

This research Unit is organized into three teams Team 1: « Biomarkers of relapse and therapeutic response in addiction and mood disorders » is an experimental and clinical research team led by Pr. Frank Bellivier, MD, PhD and Dr. Cynthia MARIE-CLAIRE, PhD.

Characterization of biomarkers throughout disease course is a key element not only to understand the pathophysiological susceptibility, refine diagnoses, improve patients’ stratification but also to monitor response and compliance.

Scientific objectives of the team:

– Identification of biological, genetic and imaging biomarkers of treatment response in mood disorders and substance use disorders to develop personalized medicine.

– implementation of prospective cohorts in order to overcome the problems generated by the retrospective evaluation of treatment response

– Implementation of multimodal approaches to better characterize the response variability in these multifactorial disorders

– Exploration and definition of disease-modifiers therapeutic strategies in mood disorders and substance use disorders

AP-HP - Bruno Etain

AP-HP (Assistance Publique des Hôpitaux de Paris) is the first academic public hospital in Paris and in France. Two Centres of Expertise in Bipolar Disorders will contribute to the recruitment and assessment of patients with bipolar disorders who will initiate lithium for the first time. The two centres are located in Fernand Widal Hospital in Paris (Pr Etain) and in Louis Mourier Hospital in Colombes (Pr Dubertret).

CIC1431 - E. Haffen

The Inserm CIC 1431 is enabling translational research. For R-Link project, firstly it participates to the prospective cohort study. Secondly, it will provide the pilot study for the evaluation of the prototype of the home-based device for Lithium level monitoring.

ACOBIOM - D. Piquemal

Acobiom is a biotechnology company specialized in the discovery of new biomarkers and in the development of new diagnostics, especially in personalized medicine applications. In R-Link program, Acobiom is engaged in competitive and sustainable biotechnology-based processes for an innovante In-Vitro Diagnostic.

ALCYM - O. Chabod

Alcym is a company focused on Design Engineering and custom Product Development in Mechatronics : a team of graduated people combining versatile skills and experience in Mechanics, Electronics and Software.

In the project R-LiNK, we will develop the pre-industrial home-based device for Lithium level monitoring. The aim is to provide patients with an easy-to use Lithium self-monitoring device.

CNRS-FEMTO institute - B. Wacogne

CNRS is the french National Center for Scientific Research. Many laboratories are joint research units of the CNRS but not only. FEMTO-ST, one of the biggest CNRS Joint Research Unit in Engineering Sciences in France, is developing a lithium self-monitoring device expected to improve patients adherence to treatment. This device will be industrialized by ALCYM (SME) and tested during a pilot study conducted by CIC 1431 (Clinical Investigation Center).

FEMTO-ST, one of the biggest labs in Engineering Sciences in France, is developing a lithium self-monitoring device expected to improve patients adherence to treatment. This device will be industrialized by ALCYM (SME) and tested during a pilot study conducted by CIC 1431 (Clinical Investigation Center).

ECRIN - A. Michon / J. Demotes-Mainard

The European Clinical Research Infrastructure Network (ECRIN, www.ecrin.org) is a sustainable, not-for-profit, distributed infrastructure with the legal status of a European Research Infrastructure Consortium (ERIC). ECRIN provides support for the development and implementation of multinational clinical research projects in Europe.

In R-LINK, ECRIN will provide services to support the sponsor in performing the clinical study in Italy, Spain, UK, Germany, Norway, Denmark and Sweden, and Poland.

Support areas include project management, regulatory and ethical submissions, monitoring and local pharmacovigilance.

INSERM TRANSFERT - D. Smagghe / B. Cagniard

Inserm Transfert SA is the private subsidiary of French National Institute of the Health and Medical research (Inserm) dedicated to technology transfer, with a department dedicated to collaborative research funding. In R-LiNK, IT will assist the coordinator in the management of the project and will provide support for the management of Intellectual property.

CEA Orsay - E. Duchesnay (WP7L) / F. Boumezbeur

Neurospin is the ultra-high field MR facility of CEA (French Alternative Energies and Atomic Energy Commission) as well as a leading research centre in Neurosciences located within the Paris-Saclay technology cluster. It is dedicated to developing, validating and applying novel methodological approaches to explore brain using MR imaging with a strong emphasis on translational research and cognitive Neurosciences.

CATI - Marie Chupin

CATI is an academic service platform supporting more than 30 multicenter neuroimaging studies in the fields of neurodegenerative diseases and psychiatry (Alzheimer, Parkinson, Huntington, ALS, Bipolar, etc.) including several therapeutic trials.
On our role in Rlink: CATI is in charge of operational aspects of MRI/MRS protocol harmonisation, MRI/MRS centre qualification and MRI/MRS data collection and quality control.

Denmark

CRD-CADIC - LV Kessing / M. Vinberg (WP8L)

Capital Region Copenhagen (CRD) has a population of 1.7 million including approx. 20.000 patients with bipolar disorder and two-thirds of these gain contact with Mental Health Services. CRDs role is to include 25 patients (WP3) including Magnetic Resonance Imaging (WP 4), Magnetic Resonance Spectroscopy (WP 5) and Blood biomarkers (WP 6). Further CRD is involved in WP 8 where the main tasks are to translate and implement the results of the R-LINK study into daily clinical life.

The role of the Institute of Copenhagen:
Clinical Recruitment Centre and Neuroimaging Centre for MRI acquisition with professor Lars Kessing leading the Copenhagen team and associated professor Maj Vinberg heading Work Package VIII on translation and implementation of R-LiNK.

Link to the CADIC web page

MONSENSO - T. Lethenborg

Monsenso is a research-driven small-medium enterprise offering a mobile Health solution that help personalise and optimise the treatment of mental disorders. Self-reported and sensor-based data of the smartphone-based solution gives a detailed overview of a patients’s mental health over time through the collection of daily outcome, adherence and behavioural data. It connects individuals, carers and health care providers to enable a data-driven personalised treatment, optimised adherence, remote care and early intervention and gives individuals reminders and advice on how to maintain good health.

Monsenso’s role in the R-LiNK project is to support clinical studies with longitudinal data collection through a customised app for the participants and web portal for clinicians and research staff. Furthermore, optimise medication adherence through medication reminders and therapeutic content.

UK

KCL - A. Young (WP3L) / B. Strawbridge

A team from the Institute of Psychiatry, Psychology & Neuroscience (King’s College London) have been coordinating the clinical assessments for R-LiNK (Work Package 3), alongside Dr Jan Scott (Newcastle), Prof Frank Bellivier and Dr Bruno Etain (Paris). The team is led by Prof Allan Young, supported by Dr Rebecca Strawbridge and Dr Diego Hidalgo-Mazzei, while Dr James Stone leads the Neuroimaging component at KCL. At our institution we have a specialist bipolar disorders clinic and we’re grateful to the clinical team for supporting study recruitment. KCL will support the other R-LiNK sites with a recruitment ‘hub’ throughout 2019 and will distribute a regular progress newsletter during this time.

UNEW - D. Cousins (WP5L)

The Institute of Neuroscience (ION) at Newcastle University has an international reputation for its work on mood disorders with a focus on their neurobiology and treatment, its neuroimaging programme enhanced through close collaboration with the Centre for In Vivo Imaging (CIVI). The Northern Centre for Mood Disorders (NCMD) is an academic-clinical collaboration established between the Institute of Neuroscience and Northumberland Tyne and Wear NHS Foundation Trust, supporting research activity, public and professional education about the mood disorders and their treatment, and promotion of best clinical practice.

Spain

IDIBAPS - E. Vieta

The IDIBAPS is a public research institute engaged in translational research in the field of biomedicine.

Furthermore, IDIBAPS is a recruiting centre and a research platform for the Hospital Clínic, where neuroimaging and biological sample analysis will be conducted.

As a consortium, IDIBAPS is formed by the Government of Catalonia, the University of Barcelona’s School of Medicine (UB), and the Institut d’Investigacions Biomèdiques de Barcelona of the Spanish Council for Scientific Research (IIBB CSIC) and the Hospital Clínic of Barcelona (HCB).

IMIM - F. Colom

IMIM/Hospital del Mar Group Description

IMIM (Hospital del Mar Medical Research Institute), located at the Barcelona Biomedical Research Park (PRBB) is, up to 82%, made up of research groups lead by professionals from the MAR Health Park , most of whom are associates of the Autonomous University of Barcelona (UAB) and the Pompeu Fabra University (UPF), as well as other seconded staff members from the Barcelona Institute for Global Health (ISGlobal), the Centre for Genomic Regulation (CRG), the Department of Experimental and Health Sciences of the Pompeu Fabra University (DCEXS-UPF) and the Barcelona Biomedical Research Park (PRBB).

At IMIM there are around 700 professionals, of whom 119 are lead researchers distributed in 60 research groups integrated into the 5 multi-disciplinary programmes framing research activities within IMIM: Cancer, Epidemiology and Public Health, Cardiovascular and inflammatory processes, Biomedical Informatics and Neurosciences.

A large proportion of its budget is provided by external competitive funds that are managed by the Mar Institute of Medical Research Foundation.

The scientific output generate from this research includes almost 945 annual papers in international journals indexed in the Science Citation Index (SCI). Another relevant fact is that 60% of the IMIM papers are published in journals that are in the top quartile of their category.

Our Mental Health Group at IMIM/Hospital del Mar has a catchment area of influence of more than 700,000 inhabitants.

The IMIM/Hospital del Mar puts together clinical research and basic science with more than 300 health staff members involved (psychiatrists, psychologists, nurses, and so forth). On the other hand, Hospital del Mar Mental Health Trust includes 5 mental health outpatient centres and 3 inpatient hospitalization areas –with more than 450 psychiatric beds- generating a permanent flow of potential subjects.

The Mental Health Group at IMIM/Hospital del Mar is coordinated by Dr Victor Pérez-Sola and Dr Francesc Colom having a special interest for affective disorders (both unipolar and bipolar), e-mental health, novel psychotherapies, trauma-related problems, suicide, edgy psychopharmacology and psychobiology.

Italy

UMIL - P. Brambilla / L. Squarcina

The University of Milan (UMIL) is a public teaching and research university, which – with 8faculties and 2 schools and a teaching staff of more than 2000 professors – is distinguished by its wide variety of disciplinary fields. A leading institute in Italy and Europe for scientific productivity, the UMIL is the largest university in the region, with approximately 64,000 students; it is also an important resource for the socio-economic context of which it is a part. As per the R-Link project, UMIL, under the coordination of Professor Paolo Brambilla and his group, will be responsible of the MRI workpackage for the investigation of connectivity and neuroplasticity changes after lithium treatment in patients suffering from Bipolar Disorder.

IRCCS - AM. Cattaneo

The IRCCS Centro San Giovanni di Dio Fatebenefratelli in Brescia is the national center of excellence for research and care in Psychiatric disorders and Alzheimer’s Disease (appointment by the Italian Ministry of Health in 1996). Its mission involves translational research, i.e. developing models of care that can be taken up by other Italian clinical centres. The Institute has a staff of 20 physicians and psychologists who treat about 2000 person with mental disorders and 4500 persons with Alzheimer’s or associated disorders yearly. Several professional researchers work in the laboratories of Biological Psychiatry, neuroimaging, genetics, neurobiology, neurophysiology and neuropsychology.

Germany

TUD - M. Bauer (WP9L)

The TUD and the Department for Psychiatry and Psychotherapy of the University Hospital Carl Gustav Carus is responsible for Communication/dissemination strategy and tools. The Team is led by Prof. Bauer and the main aim is to share all output R-LiNK elaborates on different channels to maximize the impact to be carried out. Furthermore, TUD is part of the recruiting centres where lithium MRI scans are performed.

GUF - A. Reif

Goethe University Frankfurt is one of the leading Universities in Germany. The Department of Psychiatry, Psychosomatic Medicine and Psychotherapy at the University Hospital of Frankfurt (Head: Prof. Dr. A. Reif) is uniquely and ideally suited to carry out translational research in psychiatry. Key research questions revolve around developmental psychiatry, precision medicine approaches in psychiatry including biomarker discovery, and translational psychiatry with focus on the pathophysiology of ADHD, bipolar disorder, and treatment resistant depression/suicidality. Bipolar patient enrolment and phenotyping, as planned in in the R-LiNK trial is implemented in the clinical core structure of the Department and well feasible. On site, extensive psycho- and electrophysiology phenotyping methods are established and modern neuroimaging techniques including 3T MRI and MEG are readily, MRI studies as foreseen in R-LiNK can readily be set up.
The Department features all pertinent methodological and logistical requirements, along with the necessary personal expertise, to carry out longitudinal biomarker assessments in bipolar patients as planned in R-LiNK.

LMU - T. Schulze

The multidisciplinary team of the Institute of Psychiatric Genomics and Phenomics (IPPG) is dedicated to the study of the genetics of major psychiatric disorders and of medication response. A major focus of our work lies on psychotic disorders such as schizophrenia, bipolar disorder (manic depressive illness), major depression as well as related conditions such as anxiety or substance abuse disorders. We are particularly interested in a better understanding of the high variability of the clinical presentation of mental illness, its changes over time, and its interaction with environmental factors.

JGU - M. Wessa

The research of the Department of Clinical Psychology and Neuropsychology focuses on emotional, motivational, and cognitive alterations in different mental disorders, with an emphasis on affective disorders (bipolar disorder, unipolar depression) and disorders of emotion regulation. Further, we investigate emotional and behavioral resilience mechasnisms (emotion regulation, behavioral control and immunization) enabling individuals to stay healthy despite adverse experiences. In all research projects we use experimental methods as well as multi-modal acquisition techniques (EEG, fMRI, peripheral measures, behavioral measures, self-reports). In R-LiNK we contribute our expertise in early and specific diagnosis of bipolar disorder as well as the neurobiological, cognitive and emotional characterization of bipolar subtypes.

Sweden

UGOT - M. Landen / E. Palsson

The department of Psychiatry and Neurochemistry at Sahlgrenska Academy conducts translational research, covering cell and animal models, clinical studies and extensive epidemiological research. Our research areas include bipolar disorder, addiction disorders, ageing, neurochemistry and forensic psychiatry.

Norway

UiO - O. Andreassen

The University of Oslo contributes with clinical, biological and neuroimaging data for the R-LiNK project, through recruiting centres in Oslo and Bergen.

UiB - K. Oedegaard

Haukeland University Hospital employs around 12 000 people and has a catchment area of around 450 000 people. The division of Psychiatry includes 7 different clinics covering both in and outpatient services for adults, adolescents and children. The Department of research in the division of Psychiatry is headed by Dr. Ketil J. Oedegaard who is also a Professor of Psychiatry at the Department of Clinical Medicine, University of Bergen. The division employs around 40 researchers and supporting research staff, and is responsible for a large number of ongoing research projects in all major areas of Psychiatry. The role in R-Link is to be a clinical center as a partner in the national center of excellence NORMENT. We will provide inclusion of patients, patient follow-up, collection of biological samples and MRI scans.

Scientific Advisory Board

  • Guy Goodwin, Senior Research Fellow, Department of Psychiatry at the University of Oxford. Interest in treatment of bipolar disorder and the application of neuroscience in understanding the neurobiology of mood disorders, with a focus on developing new treatments. Oxford, England
  • Anna Gonzales Pinto, Psychiatrist and professor, Division of Psychiatry Research, Santiago Apostol Hospital, Vitoria, Spain
  • John Geddes, Professor of Epidemiological Psychiatry, Director, NIHR Oxford cognitive health Clinical Research Facility, Director, Oxford Cognitive Health and Neuroscience Clinical Trial Unit, Oxford, England
  • Jair Soares, Professor and Chairman of Psychiatry and Behavioral Sciences at The University of Texas Health Science Center at Houston, TX, USA
  • Martin Alda: Professor, Department of Psychiatry, Dalhousie University, Halifax, NS, Canada

Ethics Advisory Board

  • Randall Curtis, Director, Cambia Palliative Care Center of Excellence at UW Medicine. Harborview Medical Center, University of Washington, USA
  • Nancy Kentish-Barnes, Sociologist, Famiréa Research Group, Hôpital Saint Louis, Paris, France
  • Frédéric Pochard, Psychiatrist, Clinique de Garches, France

This project has received funding from The European Union’s Horizon 2020 Research and Innovation programme Under Grant Agreement N° 754907

Prof. Frank Bellivier, MD, PhD

Department of Psychiatry and Addiction Medicine - Expert Centres Paris Diderot University
INSERM UMR-S1144
frank.bellivier@inserm.fr
Hôpital Fernand Widal 200, rue du Faubourg Saint-Denis 75475 Paris Cedex10. France
Tel Office: +33 1 40 05 42 25 / Tel Assistant: +33 1 40 05 48 69

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