Muscular and Cutaneous Dysfunction in POTS

Study Overview
=================
Brief Summary
-----------------
POTS patients seem to experience orthostasis-dependent muscle weakness and pain as well as increased muscle fatigue upon physical activity, which can be improved by regular aerobic exercise. However, reduced sweat production of the extremities with limited control of the body temperature leads to exercise intolerance, so that sticking to a training program becomes a challenge for most patients. Recordings of MVRCs provide a new tool to assess muscle membrane dysfunction, depending on ischemia, surface temperature and training. As muscle dysfunction is assumed to be present in the majority of POTS patients but has not yet been scientifically studied the present study aims at understanding the muscular and cutaneous functioning in POTS using MVRC recordings, dependent both on orthostatic stress and exercise training as well as body temperature regulation. Our main hypothesis is that POTS patients experience functional muscle dysfunction that may be linked to altered muscle perfusion or body temperature regulation. The purpose of this study is to examine muscular and cutaneous dysfunction in POTS in order to i) better understand the underlying pathology for symptoms and to ii) ultimately improve treatment options.

Detailed Description
-----------------
POTS patients seem to experience orthostasis-dependent muscle weakness and pain as well as increased muscle fatigue upon physical activity, which can be improved by regular aerobic exercise. However, reduced sweat production of the extremities with limited control of the body temperature leads to exercise intolerance, so that sticking to a training program becomes a challenge for most patients. Recordings of MVRCs provide a new tool to assess muscle membrane dysfunction, depending on ischemia, surface temperature and training. As muscle dysfunction is assumed to be present in the majority of POTS patients but has not yet been scientifically studied the present study aims at understanding the muscular and cutaneous functioning in POTS using MVRC recordings, dependent both on orthostatic stress and exercise training as well as body temperature regulation. Our main hypothesis is that POTS patients experience functional muscle dysfunction that may be linked to altered muscle perfusion or body temperature regulation. The purpose of this study is to examine muscular and cutaneous dysfunction in POTS in order to i) better understand the underlying pathology for symptoms and to ii) ultimately improve treatment options. The study includes two examination days with the same procedure for all participants. In between the examination days, participants will undergo an endurance training protocol for 14 days. The first examination day takes place in two parts: Participants will first receive repetitive MVRC recordings of the right tibialis anterior muscle (TA): 1) before, during and after repetitive stimulation of the right TA (intermittent 20Hz for 10 min) in the supine position. Then MVRC recordings will be done from the left TA 2) in the supine position and during the 60° HUT upright position for 10 minutes. The duration of this first part is approximately 60 minutes. The second part consists of a TST of the hands and feet only, including a SWT on the index, middle and ring finger of both hands. This second part also lasts about 60 minutes. On the second examination day, the first part (only 1)) of the first examination day will be repeated. In between the examination days training sessions will be undertaken on days 1, 3, 5, 7, 9 and 11 between the examination days. Participants will be asked to contract their TA muscle repeatedly by pulling the right foot towards the head in a standing position while the heel remains on the ground (at 5 second intervals). In order to carry out the training they will also receive a video demonstrating the exercise. On days 1 and 3 they will do the exercise for 5 minutes, on days 5 and 7 for 10 minutes and on days 9 and 11 for 15 minutes.

Official Title
-----------------
Muscular and Cutaneous Dysfunction in Postural Tachycardia Syndrome

Conditions
-----------------
Postural Tachycardia Syndrome

Intervention / Treatment
-----------------
* Other: Patient and Healthy Volunteers training protocol


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Patients: Informed consent as documented by signature Patients with diagnosed neuropathic POTS Age: ≥18 years and ≤ 60 years Inclusion Criteria Healthy Volunteers: Informed consent as documented by signature Age: ≥18 years and ≤ 60 years Exclusion Criteria Patients: Pregnancy and breastfeeding Inability to adhere to the training protocol Exclusion Criteria Healthy Volunteers: Pregnancy and breastfeeding Intake of vasoactive medication or known, non-treated arterial hypertension Inability to adhere to the training protocol

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients and Healthy volunteers<br>Patients and Healthy volunteers will undergo a 14-day training protocol. No study drugs will be administered. Patients and Healthy volunteers will be instructed regarding their training protocol. Training sessions will be undertaken on days 1, 3, 5, 7, 9 and 11 after the first examination day. Participants will be asked to contract their TA muscle repeatedly by pulling the right foot towards the head in a standing position while the heel remains on the ground (at 5 second intervals). In order to carry out the training they will also receive a video demonstrating the exercise. On days 1 and 3 they will do the exercise for 5 minutes, on days 5 and 7 for 10 minutes and on days 9 and 11 for 15 minutes. | Other: Patient and Healthy Volunteers training protocol<br>* Patients and Healthy Volunteers will undergo a 14-day endurance training protocol. No study drugs will be administered. Patients and Healthy Volunteers will be instructed regarding their training protocol. Training sessions will be undertaken on days 1, 3, 5, 7, 9 and 11 after the first examination day. Patients and Healthy Volunteers will be asked to contract their TA muscle repeatedly by pulling the right foot towards the head in a standing position while the heel remains on the ground (at 5 second intervals). In order to carry out the training they will also receive a video demonstrating the exercise. On days 1 and 3 they will do the exercise for 5 minutes, on days 5 and 7 for 10 minutes and on days 9 and 11 for 15 minutes.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of early supernormality in% | Change of early super normality as the most important parameter of MVRC measurements during HUT and fatigue in patients with neuropathic POTS compared to healthy subjects. | Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of relative refractory period in msec | During HUT and muscle fatigue | Day 14 | 
| Change of late supernormality period in % | During HUT and muscle fatigue | Day 14 | 
| Change of early supernormality % after Muscle endurance training | Muscle endurance training induced changes of MVRC measurements | Day 14 | 
| Change of relative refractory period in msec after Muscle endurance training | Muscle endurance training induced changes of MVRC measurements | Day 14 | 
| Change of late supernormality in % after Muscle endurance training | Muscle endurance training induced changes of MVRC measurements | Day 14 | 
| Area of palmar sweat production (in cm2) | Qualitative sweat production | Day 1 | 
| Area of plantar sweat production (in cm2) | Qualitative sweat production | Day 1 | 
| Skin wrinkling grade | Skin wrinkling grade | Day 1 | 
| Intramuscular and skin temperature change | Intramuscular and skin temperature changes during HUT and fatigue | Day 14 | 
| Recapillarization time at the lower extremities | Recapillarization time at the lower extremities before and during HUT | Day 14 | 
| Heart rate changes | Heart rate changes during HUT and fatigue | Day 14 | 
| Blood pressure changes | Blood pressure changes during HUT and fatigue | Day 14 | 
| Maximal Tibialis Anterior peak force and endurance time | Maximal Tibialis Anterior peak force and endurance time before and after training | Day 14 | 
| Circumference of the lower legs | Circumference of the lower legs before and after training | Day 14 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
POTS