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Projects: Biostatistic

Meinhardt M. MWK - Ministerium für Wissenschaft Forschung und Kunst Baden-Württemberg : Einrichtung eines 3R-Zentrums im Rhein-Neckar Raum . 12/2020-11/2025.

Reininghaus U. EU - Europäische Union 945263: IMMERSE - The implementation of Digital Mobile Mental Health in clinical care pathways: Towards person-centered care in psychiatry. 04/2021-03/2025.

The overarching aim of IMMERSE (Implementing Mobile MEntal health Recording Strategy for Europe) is to advance the transformation of mental health care in Europe into true person-centered care, focused on the needs of each individual seeking help for mental health problems, while giving them an active role in their treatment process and decision-making. In order to do so, IMMERSE has identified the Experience Sampling Methodology (ESM), a structured diary technique, as the methodology that puts the service user at the heart of their treatment. IMMERSE will integrate 20 years of research evidence on ESM into an innovative, clinical digital health tool, Digital Mobile Mental Health (DMMH), in close collaboration with stakeholders and extending it with mobile sensing data and innovative machine learning models. DMMH consists of an ESM app, assessing self-reports of mental state in daily life (ecological momentary assessment, EMA), a data-platform that allows the analysis of these data, and dashboard for visualization and feedback. IMMERSE will thoroughly evaluate strategies, processes and outcomes of DMMH implementation in a cluster Randomized Controlled Trial (cRCT) at 8 sites in 4 countries in Europe representing different contexts for implementation evaluation. At the same time, IMMERSE will identify and overcome key barriers and strengthen facilitators for implementation, transfer and scale-up of DMMH to routine mental health clinical practice by closely collaborating with relevant stakeholders, aligning the innovative DMMH tool to their needs. Similarly, the diverse ethical, legal and policy challenges and requirements will be identified and DMMH will be developed and implemented accordingly. Finally, IMMERSE is set out to do a cost-benefit analysis of the implementation and present a framework for future implementation of DMMH, including forecasting scenarios, aiming at a further scale-up of DMMH across 4 countries in Europe and beyond. IMMERSE thus offers a unique potential to significantly innovate mental health care in Europe.

Gründer G. BMBF - Bundesministerium für Bildung und Forschung 01EN2006A: EPIsoDE - Efficacy and Safety of Psilocybin in Treatment-Resistant Depression. 03/2021-02/2024.

In addition to research from the 1950s and 60s, recent modern clinical studies suggest the efficacy and safety of psilocybin, a classical psychedelic, in the treatment of depression and other psychiatric diseases. While these early results are promising, most of these studies have methodological weaknesses and shortcomings (e.g. small sample sizes), underlining the need for additional research. The proposed bicentric parallel-group study aims to investigate the safety and efficacy of oral psilocybin administered under supportive conditions in major depression in a controlled, randomized, double-blind design. Only such a study allows for firm conclusions on its efficacy, paving the way for future phase III studies. In order to ensure an appropriate control condition, the trial will investigate the efficacy of a therapeutic/high oral dose of psilocybin (25 mg) versus a low/supposedly inactive control dose (5 mg) versus 100 mg nicotinamide. We expect significant and stable treatment responses (defined as a ≥ 50% drop in the Hamilton Rating Scale for Depression; HAM-D) after the therapeutic (25 mg psilocybin) oral dose of psilocybin in comparison to active placebo (100 mg nicotinamide) and the low dose (5 mg psilocybin), while provoking only mild and transient adverse events (AE). The primary aim of the study is to examine the superiority of the 25 mg psilocybin over 5 mg and the placebo condition six weeks after the first dose. In a second step, the timing of treatment response/remission, the relative (%) change from baseline in terms of the initial value on the HAM-D scale and the question whether a second therapeutic dose (25 mg) is superior to only one therapeutic dose will be investigated.

Spanagel R. BMBF - Bundesministerium für Bildung und Forschung 01KC2004A: AhEAD Preclinical Phase II Assessment of Exosomes in Alcohol Addiction. 11/2020-10/2023.

Worldwide two billion people drink alcohol regularly. A major health consequence is alcohol addiction that is characterized by chronic relapses. Preventing relapse is the main treatment goal. Current pharmacological treatments have limited efficacy, thus better treatments and prediction approaches that can be easily translated into the clinical situation are warranted. One major hypothesis in alcohol research is that chronic alcohol intake leads to neuroinflammation that in turn triggers addictive behaviour. It has been shown that intranasal delivery of mesenchymal stem cell-derived exosomes reduces relapse behaviour in rats. Here we propose a multi-center placebo-controlled trial in rats as a preclinical confirmatory proof. We aim to confirm the hypothesis that treatment with exosomes will have long-lasting positive effects on relapse behaviour in animal models of alcohol addiction. The preclinical trial design will follow the guidelines on the development of medicinal products for the treatment of alcohol addiction provided by the European Medicines Agency (EMA), will adhere to the standards proposed for confirmatory biomedical research (Dirnagl, 2016) for nonclinical laboratory studies, and publication of the results will follow the ARRIVE guidelines. An independent third-party company focusing on the evaluation of data quality and practice in biomedical research will ensure adequate quality management and monitoring of our preclinical trial at the best possible level.

Meyer-Lindenberg A. BMBF - Bundesministerium für Bildung und Forschung 01EF1803A: RELATER - Removing language barriers in treating refugees. 03/2019-02/2023.

More than any other area of medicine, psychiatry and psychotherapy depend on successful communication. Given that most refugees arriving in Germany in the 2last years speak languages such as Arabic that are not understood by the resident therapeutic community, interpreters are scarce and not available around the clock or in emergency situations, and no financing for language services is available for many hospitals, this presents a critical obstacle in providing mental health care for refugees. This consortium will leverage recent advances in machine learning, cross-lingual communication, portable communication technologies and crosscultural psychiatry to decisively address this problem. First, we will develop a portable, secure and extensible cross-lingual communication (including speech-tospeech, speech-to-text and text-to-text translation) system, based on smartphones, to be used on site during psychiatric diagnosis in Iraqi Arabic- and Levantine-speaking refugees. This will incorporate recent technological advances to enhance diagnosis of psychiatric disorders in refugees by characterizing stress levels and psychopathology through machine-learning based tools to characterize paralinguistic features (such as prosody and voice spectral analysis) and semantic features. Diagnostic assessment will be based on an electronic version of the M.I.N.I. (International Neuropsychiatric Interview), an established structured diagnostic interview with an administration time of approximately 15 minutes that is employed in more than 100 countries. Second, we will validate this tool against the gold standard of expert diagnosis with a human translator present, establishing feasibility, reliability and validity of our approach first regionally and then nationally through a network of health care systems delivering refugee services. Third, we will extend the use of the mobile platform through building a smartphone-based app to be used by the community for logging, therapist communication, and community building, and for monitoring client’s well-being outside the clinic using ecological momentary assessment (EMA). To ensure rapid and widespread implementation into clinical practice, we will produce the necessary information for BfARM approval as a medical device. Beyond the immediate goals, our approach has potential to benefit a wide range of therapeutic and diagnostic initiatives in refugees that depend on successful communication.

Reininghaus U. DFG - Deutsche Forschungsgemeinschaft RE 3832/3-1: EMIcompass - Efficacy of a novel, accessible, transdiagnostic, compassion-focused ecological momentary intervention for enhancing resilience in help-seeking youth. 12/2018-11/2021.

Most mental disorders first emerge in youth and, as such, contribute substantially to global disease burden. In recent years, this has become particularly evident for psychotic disorders, for which risk manifests already at a developmentally earlier stage in the form of subclinical psychotic experiences. Contemporary research further suggests that subclinical psychotic experiences often co-occur with anxiety, depression and mania, reflecting a transdiagnostic phenotype associated with a range of subsequent psychopathological outcomes. Elevated stress sensitivity is one of the most widely studied psychological mechanism underlying psychotic and affective mental health problems. Thus, screening for, and targeting stress sensitivity as an underlying mechanism of, this transdiagnostic phenotype in youth is a promising indicated and translational strategy for preventing adverse outcomes later in life. Psychological help, however, remains difficult to access for youth and has limited efficacy under real-world conditions, calling for novel approaches. Compassion-Focused Interventions (CFIs) offer a wide range of innovative therapeutic techniques for targeting stress sensitivity and enhancing emotional resilience in psychosis, especially when co-occurring with affective disturbances. What is more, the recent rapid technological advances provide a unique opportunity to deliver youth-friendly, accessible, personalized, real-time, mobile health (mHealth) interventions, most prominently, ecological momentary interventions (EMIs) that enable youth to access interventions that are tailored to what a young person needs in a given moment and context in daily life. EMIs further allow for investigating several causal criteria of candidate underlying psychological mechanisms, but robust, trial-based evidence on these interventions remains very limited. The project aims to examine the efficacy and clinical feasibility of a novel, accessible, transdiagnostic, ecological momentary, compassion-focused intervention for improving emotional resilience to stress (EMIcompass) in help-seeking youth. In an exploratory randomized controlled trial, youth aged 12-25 with psychotic, depressive, anxiety, and/or manic symptoms presenting to mental health services of the Central Institute of Mental Health, Mannheim, will be randomly allocated to the EMIcompass intervention in addition to treatment as usual (TAU) (experimental condition) or a control condition of TAU only. Stress sensitivity, emotional resilience, psychotic, depressive, anxiety and manic symptoms will be the primary outcomes obtained at baseline, post-intervention, and 4-week follow-up. Ecological interventionist causal models will be tested to improve our understanding of several causal criteria of underlying psychological mechanisms and contribute to enhancing efficacy of mHealth interventions for promoting resilience in youth, with the ultimate goal of preventing adverse outcomes later in life.

BMBF - Bundesministerium für Bildung und Forschung 01KG0822: SIMaMCI-Study: Trial of Simvastatin in Amnestic Mild Cognitive Impairment (MCI) Patients (statistics). 01/2009-12/2013.

Die hemmende Wirkung von Statinen auf das Fortschreiten der Alzheimer Krankheit bei Patienten mit leichter kognitiver Beeinträchtigung (Mild Cognitive Impairment=MCI) ist bisher nur unzureichend beschrieben. Dies im Rahmen einer klinischen Studie herauszufinden haben sich die Charité als Sponsor im Sinne des Arzneimittelgesetzes sowie verschiedene Prüfzentren gemeinsam zum Ziel gesetzt.

Zentralinstitut für Seelische Gesundheit (ZI) - https://www.zi-mannheim.de