EUCLID

Mental, cognitive, visual, and hearing health issues among older adults are among the top 10 public health challenges in Europe. They frequently occur simultaneously and have a cumulative negative effect on quality of life and mental well-being.

To mitigate this negative impact and promote mental well-being—particularly by taking into account gender and minority perspectives—SENSE-Cog aimed to:

1. Understand the interactions between sensory impairments, cognitive functioning, and mental health;
2. Identify new screening and detection methods for diagnostic and therapeutic purposes;
3. Translate this knowledge into clinical applications for the mental well-being of European citizens.

Methods:

SENSE-Cog employed a “mixed-methods” approach with a trans-European collaboration, led by the United Kingdom, involving 7 EU countries, academics, SMEs, municipal administrations, and patient and public representatives. The project will be structured into interconnected Work Packages (WPs), reflecting 7 thematic areas:

1. Exploration: epidemiological analysis of five major European longitudinal databases to identify risk profiles associated with good or poor mental health outcomes;
2. Assessment: adaptation and validation of assessment tools for cognition and sensory impairments in vulnerable populations, including the development of a composite e-screen for sensory, cognitive, and mental functioning;
3. Intervention: clinical trial of a new sensory support intervention;
4. Engagement: Establishment of a European network of public and patient engagement to inform the WPs and disseminate results;
5. Valorization: economic and cost-effectiveness analyses;
6. Management, governance, and ethics.

Impact:
SENSE-Cog will promote the early detection of sensory, cognitive, and mental impairments, enabling rapid intervention, preventing deterioration, and limiting negative impacts on the well-being of older adults.

Publications / Results:

• Regan J, Frison E, Collin F et al. and for the SENSE-Cog Trial Development Team. Individualized sensory intervention to improve quality of life in people with dementia and their caregivers (SENSE-Cog trial): study protocol for a randomized controlled trial. Trials. January 25, 2019;20(1):80
• Hooper E, Simkin Z, Abrams et al. Feasibility of an Intervention to Support Hearing and Vision in Dementia: The SENSE-Cog Field Trial. JAGS. Apr 29, 2019
• Leroi I et al. Impact of an intervention to support hearing and vision in dementia: The SENSE-Cog Field Trial. International Journal of Geriatric Psychiatry. Nov 7, 2019
• Leroi I, Armitage CJ, Collin F et al. and the SENSE-Cog Work Package 3 investigators. A randomized controlled trial of hearing and vision support in dementia: Protocol for a process evaluation in the SENSE-Cog trial. Trials. 2020;21(1):223
• Leroi I et al. Hearing and vision rehabilitation for people with dementia in five European countries (SENSE-Cog): a randomized controlled trial. Lancet Healthy Longev. Nov 2024;5(11):100625
• Alexopoulos P, Demertzis AA, Biris P et al. Pragmatic questionnaire-based evaluation of auditory function in individuals with major neurocognitive disorders and hearing loss in diverse contexts. Front Aging Neurosci. June 13, 2025;17:1504358. doi: 10.3389/fnagi.2025.1504358. PMID: 40584182; PMCID: PMC12202519.
• Paterson, Luke, Rachel A. Elliott, Fofi Constantinidou, et al. 2025. “The Cost-Effectiveness of an Intervention to Preserve Independence in People With Dementia (Vs. No Intervention): A Decision-Analytic (Markov) Model Analysis.” International Journal of Geriatric Psychiatry: e70132
• Alison Holden, Catherine Molony, Chris Armitage, et al. Delivering a hearing and vision support intervention for people with dementia: looking “under the hood” of the SENSE-Cog trial before and during the COVID-19 pandemic. Disabil Rehabil 2026 May 29:1–23. doi: 10.1080/09638288.2026.2676067. PMID: 42212629

A project funded by the European Commission as part of IMI2, comprising several trials sponsored by Janssen Vaccines and Prevention .

The objective of the study was to evaluate the safety, tolerability, and immunogenicity of three heterologous prime-boost regimens for the Ad26.ZEBOV and MVA-BN-Filo Ebola vaccines. The study included healthy adults and older participants, people living with HIV, and healthy children divided into two age groups.

EBOVAC2 received the “Star of Europe” Special Jury Prize awarded by the French Ministry of Research in 2021. This award aims to recognize and highlight the European commitment of research teams that have distinguished themselves through the success of their projects.

Publications / Results:

• Barry H, Mutua G, Kibuuka H, et al.; EBL2002 Study Group. Safety and immunogenicity of a 2-dose heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola vaccination in healthy and HIV-infected adults: A randomized, placebo-controlled Phase II clinical trial in Africa. PLoS Med. Oct. 29, 2021;18(10):e1003813. doi: 10.1371/journal.pmed.1003813. PMID: 34714820; PMCID: PMC8555783.
• Anywaine Z et al. Safety and immunogenicity of a 2-dose heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola vaccination in children and adolescents in Africa: A randomized, placebo-controlled, multicenter Phase II clinical trial. PLoS Med. 2022 Jan 11;19(1):e1003865.

PRIMALVAC is a placental malaria vaccine candidate derived from VAR2CSA, designed to prevent severe clinical complications associated with Plasmodium falciparum infection during pregnancy. The objective of the PRIMALVAC trial (Sponsored by Inserm) was to evaluate the safety and immunogenicity of PRIMALVAC adjuvanted with Alhydrogel or a stable glucopyranosylated lipid emulsion adjuvant (GLA-SE) in non-pregnant women from France and Burkina Faso.

PRIMALVAC was a first-in-human trial, randomized, double-blind, placebo-controlled, dose-escalation trial conducted in two sequential phases: a Phase Ia study in women aged 18 to 35 years, malaria-naive, at a hospital in France, followed by a Phase Ib study conducted in nulliparous women naturally exposed to P. falciparum at a clinical site of a research center in Burkina Faso.

Publications / results:

• Sirima SB, Richert L, Chêne A, et al. PRIMVAC vaccine adjuvanted with Alhydrogel or GLA-SE to prevent placental malaria: a first-in-human, randomized, double-blind, placebo-controlled study. Lancet Infect Dis. May 2020;20(5):585-597. doi: 10.1016/S1473-3099(19)30739-X. Epub 2020 Feb 4. PMID: 32032566.

This study, conducted in collaboration with the NS-PARK network, is a French, multicenter, parallel-group, two-arm, randomized, placebo-controlled, double-blind, Phase II proof-of-concept (POC) clinical trial sponsored by the Toulouse University Hospital, evaluating the effect of lixisenatide in patients with early-stage Parkinson’s disease (PD). This randomized, double-blind clinical trial aimed to evaluate the effects of lixisenatide, compared with placebo, on the motor and non-motor symptoms of PD in patients with early-stage disease.

Publications / Results:

• Meissner WG et al. Trial of Lixisenatide in Early Parkinson’s Disease. 2024. The New England Journal of Medicine. 390. 1176–1185.

The PREVAC trial is a Phase IIb randomized controlled trial evaluating the safety and immunogenicity of three vaccine strategies that may prevent Ebola virus disease (EVD) in children and adults in four West African countries (Guinea, Mali, Sierra Leone, and Liberia). As part of this consortium, the trial is sponsored by Inserm, the NIH NIAID, and the LSHTM. Participants are randomized to receive either the Ad26.ZEBOV (rHAd26) vaccine with an MVA-BN-Filo (MVA) booster, the rVSVΔG-ZEBOV-GP (rVSV) vaccine with or without a booster, or a placebo.

Long-term follow-up (M60) of participants—conducted with a high retention rate as part of the EDCTP2-funded PREVAC-UP project—is currently being analyzed.

Publications / results:

• Badio M, Lhomme E, Kieh M, et al.; PREVAC study team. Partnership for Research on Ebola Vaccination (PREVAC): protocol of a randomized, double-blind, placebo-controlled phase 2 clinical trial evaluating three vaccine strategies against Ebola in healthy volunteers in four West African countries. Trials. Jan. 23, 2021;22(1):86. doi: 10.1186/s13063-021-05035-9.
• Lévy Y, Lane C, Piot P, Beavogui AH, et al. Prevention of Ebola virus disease through vaccination: where we are in 2018. Lancet. September 1, 2018;392(10149):787-790. doi: 10.1016/S0140-6736(18)31710-0. Epub 2018 Aug 10. PMID: 30104048; PMCID: PMC6128979.
• Lhomme E, Modet C, Augier A, et al; PREVAC study team. Enrolling study personnel in Ebola vaccine trials: from guidelines to practice in a non-epidemic context. Trials. July 11, 2019;20(1):422. doi: 10.1186/s13063-019-3487-0. PMID: 31296253; PMCID: PMC6624937.
• Badio M, Lhomme E, Kieh M et al. Partnership for Research on Ebola Vaccination (PREVAC): protocol of a randomized, double-blind, placebo-controlled phase 2 clinical trial evaluating three vaccine strategies against Ebola in healthy volunteers in four West African countries. Trials. Jan. 23, 2021;22(1):86
• PREVAC Study Team. Randomized Trial of Vaccines for Zaire Ebola Virus Disease. N Engl J Med. Dec. 29, 2022;387(26):2411–2424
• Andrew W. Lee; Ken Liu, Edouard Lhomme et al.; PREVAC study team.  Immunogenicity and vaccine shedding after 1 or 2 doses of the rVZVΔG-ZEBOV-GP Ebola vaccine (ERVEBO®): Results from a phase 2, randomized, placebo-controlled trial in children and adults. 2023. Clinical Infectious Diseases. 78. 870–879
• Wiedemann A, Lhomme E et al. Long-term cellular immunity following vaccination against Zaire Ebola virus disease. Nat Commun. September 3, 2024;15(1):7666. 
• Simon Valayer, Marie Alexandre, Mélanie Prague et al.; PREVAC study team. Evaluation of waning of IgG antibody responses after rVSVΔG-ZEBOV-GP and Ad26.ZEBOV, MVA-BN-Filo Ebola virus disease vaccines: a modeling study from the PREVAC randomized trial. 2025. Emerging Microbes & Infections. 14. 0
• Ange-Marie D Kpetigo, Marie Alexandre, Aboubacar Camara et al. Effect of the time of day for vaccination on the immune response to Ebola virus disease vaccines: A modeling study from the PREVAC randomized trial. 2026. PLOS Neglected Tropical Diseases. 20. E0013950.

Over a 5-year period, the objectives of the IP-cure-B (H2020) project are to conduct a proof-of-concept clinical trial, sponsored by ANRS MIE, to evaluate new immunomodulatory strategies aimed at strengthening innate immunity and remodeling the immune environment of the infected liver, in order to improve adaptive immunity and the response to stimulation by a therapeutic vaccine

This is an exploratory, open-label, multicenter, randomized Phase II study designed to determine whether, in patients with chronic hepatitis B who are non-cirrhotic, AgHBe-negative, and virologically controlled, discontinuation of NUC therapy or discontinuation of NUC therapy following administration of SLGN increases the rate of HBsAg seroconversion compared with standard treatment for chronic hepatitis B (currently approved NUC-based treatments will be permitted, namely tenofovir/TDF, tenofovir/TAF, and entecavir). Exploratory analyses will help determine whether changes in the liver’s immune environment are responsible for the decrease in HBsAg.

Participants are being recruited at several centers specializing in hepatology across Europe in four countries (Germany, Spain, France, and Italy).

Participants are randomized to one of the following groups: “control” (arm A), “discontinuation of NUC treatment” (arm B), or “discontinuation of NUC+SLGN treatment” (arm C). The control arm will receive only NUC treatment for the duration of the trial. In arms B and C, participants will be followed for 48 weeks after discontinuing treatment. Clinical and laboratory parameters will be monitored. The safety of participants randomized to each arm will be continuously monitored, and temporary halt criteria will be defined in the protocol so that ad hoc meetings of the Data Safety Monitoring Board (DSMB) “Data Safety Monitoring Board”) can be convened in the event of safety-related issues.

The overall objective of this European project (H2020) is to demonstrate, over the course of a 5-year project, that isolation of the pulmonary veins using pulsed electric field (PEF) ablation is more effective than radiofrequency ablation, which is currently the gold standard treatment.

As a reminder, PEF uses high-voltage electrical micro-shocks to create nanometric pores in cell membranes, without causing collateral damage to non-cardiac tissues.

The project aims to demonstrate that PEF is faster, more effective, and safer than radiofrequency ablation.

To this end, two separate randomized clinical trials, sponsored by the Bordeaux University Hospital, were conducted to provide evidence of PEF’s superiority in paroxysmal atrial fibrillation and its potential efficacy in persistent atrial fibrillation:

• BEAT-AF PAROX: Innovative electroporation procedure for the treatment of paroxysmal atrial fibrillation
• BEAT-AF PERS: Innovative electroporation procedure for the treatment of persistent atrial fibrillation

These first two clinical trials will pave the way for a larger-scale efficacy trial aimed at confirming and expanding on the results of BEAT-AF, and definitively establishing PEF as the gold standard in international guidelines.

Publications / Results:

• Erhard N, Frison E, Asselineau J, Aouar B et al. Comparing pulsed-field electroporation and radiofrequency ablation for the treatment of paroxysmal atrial fibrillation: design and rationale of the BEAT PAROX-AF randomized clinical trial. 2024. Europace. 26. Euae103.
• Pierre Jais, Petr Neuzil, Daniel Scherr et al. Pulsed-field vs. radiofrequency ablation for paroxysmal atrial fibrillation: the BEAT PAROX-AF trial. 2026. European Heart Journal. Ehaf1115.