Please select the eligibility criteria that correspond to the clinical trial below.
Title: Intensity-dependent Impacts of Training on Growth Factors BDNF and Cognitive Functions in Persons With Multiple Sclerosis - a Single-center Randomized Controlled Trial
Brief Summary: Multiple Sclerosis (MS) is a chronic immune-mediated disease of the central nervous system, accompanied by varying inflammatory manifestations, demyelinization and axonal loss. With chronic progressive or relapsing-remitting disease onsets persons with MS (pwMS) progressively develop impaired functional capacity and show reduced physical activity and cognitive decline compared to healthy controls. The primary aims of rehabilitation in pwMS are therefore to increase levels of activity and participation leading to increase independence of the participants. In general exercise ranges from passive physiotherapy-based interventions to submaximal endurance training sessions. Current recommendations advise pwMS that exercise should be matched with the individual performance capacities. Exercise training in pwMS then has the potential to target and improve many components outlined in the ICF-model.

Cytokines and neurotrophic factors have received increased attention in MS research and addressed the brain-derived neurotrophic factor (BDNF) as an important mediator of neuronal regeneration linking the effects of exercise with MS pathogenesis. Data show positive connections between elevated neurotrophin concentrations, induction of neuroplasticity, recovery of the motor and cognitive functions and the applied training intensities. Similarly, intensive and progressive exercise bouts seem to have greater benefits on cardiorespiratory fitness and maximum voluntary strength in elderly and seniors with dementia. Therefore, specific exercise prescriptions may be necessary for targeting the specific impairments also in pwMS.

This study aims to evaluate two different training modalities (intensive versus normal) in pwMS. It is expected that both modalities will improve cardiorespiratory fitness and cognitive functions in pwMS. Based on the findings that higher training intensities facilitate greater benefits, it is expected that pwMS will tolerate the intensive training intensities and show positive connections to elevated neurotrophin concentrations.

The results will to help to clearer understand the benefits of each type of exercise conveyed for pwMS and will assist in the development of patient-specific exercise prescriptions.


Options:
A: Inclusion Criteria:

* MS defined according to the McDonald criteria revised in 2010
* Men and women aged between 18 and 65 years
* RR and SP forms
* Duration of progression ≤ 25 years
* EDSS ≤ 5.5
* Lack of disease activity as defined by the new Lublin criteria (2013)
* Cognitive complaint and/or cognitive disorders according to the investigator's judgement
* Impaired cognitive performance at least 1.65 SD below normative data at one test of the BCcogSEP battery
* French native language
* Owner of a laptop computer with Internet access
* Signing of the informed consent

Exclusion Criteria:

* - Other neurological, psychiatric or developmental diseases prior to the MS diagnosis
* Cranial trauma sequelae
* Chronic alcohol and/or drug consumption
* EDSS \> 6
* Relapse and/or treatment with corticosteroids within the past month
* Persons deprived of liberty, minors, adults under wardship
* Cognitive examination within the past 6 months (including in particular all or some of the tests proposed by this project)
* Presence of dementia according to DSM V criteria, or of cognitive disorders preventing the patient from undergoing cognitive tests or performing cognitive rehabilitation exercises
* Any visual or motor deficit preventing the patient from undergoing cognitive tests or performing cognitive rehabilitation exercises
B: Inclusion Criteria:

* Ages 18-70
* Definite MS Diagnosis, any subtype \[83\]
* Probable cognitive impairment as defined by a score ≤ 1 SD below the mean of normative data on the SDMT
* Concurrent medications to be kept constant over three months (as possible)
* No relapse or steroids in previous month
* Reading score on WRAT-3 of 37 or greater
* Visual, auditory and motor capacity to operate computer software, as judged by treating neurologist or study staff
* Willing to sign Agreement to Borrow Laptop

Exclusion Criteria:

* History of mental retardation, pervasive developmental disorder or other neurological condition associated with cognitive impairment
* Primary psychiatric disorder that would influence ability to participate
* Other serious uncontrolled medical condition (e.g., cancer or acute myocardial infarction)
* Alcohol or other substance use disorder
* History of computer-based training manufactured by Posit Science
* Learned English language after 12 years of age
C: Inclusion Criteria:

* Diagnosis of Multiple sclerosis

Exclusion Criteria:

* Diagnosis of other neurological conditions
D: Inclusion Criteria:

Key inclusion criteria for the participants' eligibility are a definite MS diagnosis (McDonald criteria). Participants fulfilling the key inclusion and the following criteria are eligible for this study

* EDSS 1.0 - 6.0
* Age 19 - 75 years

The presence of any one of the following exclusion criteria will lead to exclusion of the participant:

* Persistent infections
* Severe cardiovascular and pulmonal diseases (renal failure, hepatic dysfunction, cardiovascular disease)
* Severe cardiovascular exacerbations (RR \> 240/120, HR above the age predicted maximum of 220-Age) during training
* Immunosuppressive therapy the day of CPET
* Life style factors and / or persistent addictions (drug or alcohol abuse)
* Inability to follow the study procedures (due to psychological disorders or dementia)
* Insufficient knowledge of the project language (German)
* Women who are pregnant or breast feeding,
* Intention to become pregnant during the course of the study,
* Lack of safe contraception, defined as: Female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases.
* Participation in another study with investigational drug within the 30 days preceding and during the present study,
* Previous enrolment into the current study,
* Enrolment of the investigator, his / her family members, employees and other dependent persons,
* Specific exclusions for the disease under study,
* Specific concomitant therapy washout requirements prior to and/or during study participation,
* Dietary restrictions

Exclusion Criteria: Criteria in which the participant withdraws from this study may be the following:

* Inability to comply with the daily schedule
* Strong symptom exacerbations
* Withdrawal of informed consent
* Non-compliance
* Disease progression or relapse

Answer: D