Projects Funded - Clinical
FACILITATING PATIENT STUDIES - "CLINICAL"
**UPDATED RESULTS** "Abdominal Binders to treat Orthostatic Hypotension in Multiple System Atrophy": Gregor Wenning, MD, PhD & Alessandra Fanciulli & Cecilia Raccagni (Medical University of Innsbruck, Austria)
MSA Coalition Grant #2020-05-002 – $50,000
Orthostatic hypotension (OH) is a key feature of multiple system atrophy (MSA). It is characterized by severe blood pressure drops upon standing and worsens quality of life by causing recurrent spells of dizziness, blackouts and falls. Drugs to treat OH can cause high blood pressure in the supine position, often limiting an effective treatment of OH itself. In patients with OH due to Parkinson’s disease, we showed that elastic abdominal binders combat OH, without inducing high blood pressure when lying down. Regular use of abdominal binders also significantly improved OH-related symptoms in daily life.
In MSA, the efficacy of elastic abdominal binders in treating OH has yet to be evaluated. It is also unclear, whether an optimized control of OH can ameliorate gait performance and global mobility in daily living. In this study, born from the cooperation between the Medical University of Innsbruck (Austria) and the Radboud University of Nijmegen (Netherlands), we plan to recruit 30 patients with the Parkinson variant of MSA to test whether wearing an elastic abdominal binder: i. reduces the fall in blood pressure upon standing; ii. improves gait performance, as measured by wearable sensors; iii. is safe and tolerable.
In a home-based setting of the study, we also plan to verify whether wearing an elastic abdominal binder for five consecutive days: i. ameliorates OH symptoms in daily living; ii. raises the blood pressure upon standing; iii. increases the number of walking bouts measured by physical activity wearable sensors. If their efficacy were confirmed, abdominal binders would represent a useful OH therapy for those patients with supine high blood pressure or at risk of developing it (ca. 50% of MSA patients). If wearable sensors were able to detect an improvement in gait and mobility, they may be applied to evaluate the functional impact of future OH therapies.
1. Progress Report July 15, 2021 submitted by Prof. Dr. Gregor Wenning
Orthostatic hypotension (OH) is a key feature of multiple system atrophy (MSA) and affects about every third individual suffering Parkinson’s disease (PD). OH is characterized by blood pressure (BP) falls, which occur upon standing and significantly worsen quality of life by causing recurrent spells of dizziness, light-headedness, blackouts and falls. Drugs to treat OH can cause high blood pressure in the supine position, often limiting an effective treatment of OH itself. Elastic abdominal binders act in a physical, non-pharmacological way by applying pressure to the abdominal wall, therefore limiting venous blood pooling in this area. As a result, an increase in venous return to the heart should lead to BP stabilization upon standing, and subsequently to a reduction of severity or even prevent occurrence of orthostatic symptoms.
In people with OH due to PD, it was already shown that elastic abdominal binders combat OH, without inducing high blood pressure when lying down. Regular use of abdominal binders also significantly improved OH-related symptom burden in daily life and was overall well-tolerated. In MSA, the efficacy and safety of elastic abdominal binders in treating OH has yet to be evaluated. It is also unknown, whether an optimized control of OH can ameliorate gait performance and global mobility in daily living of people with Parkinsonian syndromes.
The “Abdominal Binders to treat Orthostatic Hypotension in Parkinsonian Syndromes (ABOH-PS)” study is a monocentric, randomized, placebo-controlled, double-blinded, crossover phase II clinical trial with an open-label treatment-extension phase, conducted at the Department of Neurology, Medical University, Innsbruck, Austria. The study team, led by MSA-experts Prof. DDr. Gregor K. Wenning (principle investigator) and DDr. Alessandra Fanciulli (project co-coordinator), as well as gait-expert DDr. Cecilia Raccagni (project co-coordinator), aims to recruit 30 individuals with symptomatic OH due to either the Parkinson variant of MSA or PD to test whether wearing an elastic abdominal binder:
- reduces the fall in BP upon standing;
- improves gait performance (measured by wearable sensors); and
- is safe and tolerable.
In a home-based setting of the study, it is additionally planned to verify whether wearing an elastic abdominal binder for five consecutive days:
- ameliorates OH symptoms in daily living;
- raises the BP upon standing;
- increases the number of walking bouts measured by physical activity wearable sensors.
If their efficacy were confirmed, elastic abdominal binders would represent a useful OH therapy for those individuals with supine high BP or at risk of developing it (approximately 50%), or individuals on polypharmacy. If wearable-sensors were able to detect an improvement in gait and mobility, they may be applied to evaluate the functional impact of future OH therapies.
With the financial support of the MSA Coalition, this project was officially started January 1st, 2021. After finalization of the research protocol and the clarification of administrative and regulatory aspects (approval of the Innsbruck’s ethical committee, clinic direction, trial center, as well as the Austrian Federal Office for Safety in Health Care), the active recruitment process started in May 2021.
A schematic illustration of the study procedures is given in the following figure.
“Inside the gait – a new era on the horizon for atypical parkinsonian disorders”: Gregor K. Wenning, MD, PhD (Medical University of Innsbruck, Austria)
MSA Coalition Grant #2016-09-008 – $50,000
Multiple system atrophy (MSA) and Progressive Supranuclear Palsy (PSP) are rare and devastating neurological conditions. There is currently no therapy that can halt or slow the progression of these diseases. Clinical trials with a large number of patients are urgently needed to test the efficacy of therapeutic agents. In addition, an early and reliable diagnosis of MSA and PSP and the discrimination of these diseases from the more benign idiopathic Parkinson’s disease can be a challenge for the neurologist, especially at early stages.
Emerging data show that instrumented gait analysis using wearable sensors can provide a great amount of clinically relevant information which could help to better characterize these diseases and to quantify their progression characteristics and rates in an objective, rater-independent way. Moreover, new findings show that these sensors may be able to detect risk-of-fall associated gait parameters. This is particularly relevant in the clinical assessment and in the follow-up of patients with atypical parkinsonian disorders where the gait impairment and the risk of fall are even more prominent compared to idiopathic Parkinson’s disease.
Based on emerging findings in favor of the feasibility of wearable sensors in the clinical practice, we aim to propose a new objective tool in the diagnostic workup, individualized progression assessment, and therapeutic response of atypical parkinsonian disorder patients.
2. Presentation (June 2019): The Diagnostic Scope of Sensor-Based Gait Analysis in Atypical Parkinsonism
3. Published Article (May 2019): Gait and postural disorders in parkinsonism: a clinical approach
4. Published Article (January 2019): The Diagnostic Scope of Sensor-Based Gait Analysis in Atypical Parkinsonism: Further Observations
5. Published Article (June 2018): Sensor-based gait analysis in atypical parkinsonian disorders.
6. Conclusions and Outlook (View Full Final Report – December 2018)
Our study addressed the primary research question whether MSA patients can benefit from a standardized physiotherapy based on guidelines for PD. Additionally, the study aimed to investigate whether physiotherapy effects are sustainable. The most important clinically relevant finding was that gait of MSA patients is improving after an intensive in-hospital in-patient physiotherapy program. Thinking further, this finding after such a short treatment duration is even surprising in relation to the motor impairment of MSA patients. Still, most of these therapeutic effects were not significantly worsening after a low-dose unsupervised in-home training program. However, our data indicate a
tendency not to maintain the same improvement levels showed after an intensive physiotherapy in-hospital. Therefore, an intensive in-patient in-hospital physiotherapy seems to be a more effective intervention than a low-dose in-home training. There are several possible explanations for this result. Firstly, it may be hypothesized that patients at home without supervision of an expert are not
performing the training program properly. Secondly, it may reflect that patients do not have enough time during the 5-day long in-hospital physiotherapy to learn properly the training program and being able to reproduce it correctly at home. Another possible explanation is the lack of compliance and adherence to the training plan.
The current study was the first-ever assessment of physiotherapy in MSA patients. Further studies are needed to confirm and implement our results. For patients with PD, there is strong evidence that the introduction of an activity coach in the intervention plan, who guides patients towards a more active lifestyle through periodic coaching sessions enhances patients´ motivation and promotes
physical activity . Therefore, an activity coach may educate patients about the benefits and the importance of physical activity, may help to overcome any perceived barriers to engaging in physical activity and set systemic goals, therefore improving patients´ motivation, well-being and levels of independence.
“Global MSA Registry & Study Group”: Florian Krismer, M.D. (Innsbruck Medical University, Austria) and Lucy Norcliffe-Kaufmann, Ph.D. (New York University NY)
MSA Coalition Grant #2018-12-001 – $38,600
MSA Coalition Grant #2017-10-001 – $30,000
MSA Coalition Grant #2016-09-001 – $60,000
MSA Coalition Grant #2015-04-001 – $50,000
MSA Coalition Grant #2013-12-001 – $44,232
This project aims to establish the first-ever global registry dedicated to Multiple System Atrophy patients. Facilitating future worldwide clinical trials, the registry will be used to notify all patients that meet study entry criteria for clinical trials in MSA on an international scale. The registry will also provide a means for sharing anonymous patient information to define the disease specific characteristics and establish the definitive natural history of MSA. Registered patients will be followed thoroughly and periodically to identify potential biological markers of disease risk and severity in a global, worldwide longitudinal prospective study.
1. Published article (April 2015): “Multiple System Atrophy: The case for an international collaborative effort”