Clinical trial NCT02608424: Effects of Feet Mechanical Stimulation on Cardiovascular Autonomic Profile and Inflammation in Parkinson's Disease
Official title: Effects of Feet Mechanical Stimulation on the Inflammatory State and Cardiovascular Autonomic Profile in Patients With Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Parkinson's Disease
Autonomic Neuropathy
Inflammation
Hypertension
Keywords: Foot mechanical stimulation
Autonomic nervous system
Inflammation
Parkinson's disease
Spectral analysis
Heart rate variability
Blood pressure variability
Lead sponsor: Istituto Clinico Humanitas
Sponsor class: OTHER
First posted: 2015-11-18
Enrollment: 50
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: In the present study, investigators test the hypothesis that a controlled mechanical pressure applied on specific sites of both fore-feet (ES) can reduce the inflammatory state and arterial blood pressure in patients with Parkinson's Disease by increasing the overall parasympathetic activity and reducing vascular sympathetic modulation.

Detailed description: Neuroinflammation may contribute to the cascade of events leading to neuronal loss in Parkinson's disease (PD) thus facilitating motor and autonomic impairment. A link between autonomic function and chronic and acute inflammation has been previously described. Specifically, active inflammatory state was associated with an overall increased sympathetic tone, whereas the parasympathetic cholinergic activation seemed to promote a decrease of inflammatory compounds in inflamed tissues. In addition, a functional link between peripheral sensory afferents and autonomic control has been reported. In a recent study it was observed that in PD patients a somatosensory activation by mechanical stimulation of specific sites of the fore-foot (effective stimulus, ES), improved gait, increased cardiac vagal modulation and decreased vascular sympathetic activity at rest. This latter effect was associated with a decline in arterial blood pressure values.

The present study is aimed at:

* Addressing the magnitude of the inflammatory state in PD patients.
* Testing the hypothesis that a change in the autonomic profile of PD patients induced by ES, consistent with cardiovascular increased parasympathetic and decreased sympathetic activities, may promote an overall reduction of the PD inflammatory state.

Eligibility criteria: Inclusion Criteria:

* Idiopathic PD characterized by a moderate/important motor impairment (Hoehn\&Yhar scale 2-4)
* PD will be diagnosed according to the United Kingdom (UK) Parkinson's Disease Society Brain Bank criteria, (or on the basis of clinical criteria, Dopamine Transporter (DAT)- scan and/or MRI).

Exclusion Criteria:

* Dysautonomias and other neurodegenerative diseases
* History/familiarity with seizures
* Atrial fibrillation and other relevant cardiac rhythm disturbances
* Chronic inflammatory diseases and chronic use on anti-inflammatory drugs
* Diabetes
* Other neurological or psychiatric diseases
* Pacemakers or other electronic implants inserted into the body
* Coronary disorders, elevated intracranial blood pressure
* Assumption of drugs facilitating seizures, psychiatric drugs, alcohol abuse

Primary outcomes:
measure: Changes of Pentraxin 3 (PTX3) plasma levels induced by feet mechanical stimulation.
timeFrame: Blood samples will be collected at Baseline, and 16 days from baseline (after 5 feet mechanical stimulation sessions).
measure: Changes of Interleukine-6 (IL-6), plasma levels induced by feet mechanical stimulation.
timeFrame: Blood samples will be collected at Baseline, and 16 days from baseline (after 5 feet mechanical stimulation sessions).
measure: Changes of Tumor Necrosis Factor (TNF) plasma levels induced by feet mechanical stimulation.
timeFrame: Blood samples will be collected at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
measure: Changes of C Reactive Protein (CRP) plasma levels induced by feet mechanical stimulation.
timeFrame: Blood samples will be collected at Baseline, and 16 days from baseline (after 5 feet mechanical stimulation sessions).
measure: Changes of Heart Rate (HR) values in supine position induced by feet mechanical stimulation.
timeFrame: HR will be assessed in beats/min at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
measure: Changes of Blood Pressure (BP) values in supine position induced by feet mechanical stimulation.
timeFrame: BP will be assessed in mmHg at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
measure: Changes of the index of cardiac vagal modulation (HFRR, High Frequency oscillatory component of R-R interval (RR) variability at ~0.25Hz) in supine position induced by feet mechanical stimulation.
timeFrame: HFRR will be assessed in msec2 at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
measure: Changes of the index of cardiac sympathetic modulation (LFRR, Low Frequency oscillatory component of R-R interval variability at ~0.10 Hz) in supine position induced by feet mechanical stimulation.
timeFrame: LFRR will be assessed in msec2 at baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
measure: Changes of the index of cardiac sympatho-vagal modulation (LF/HF)RR in supine position induced by feet mechanical stimulation.
timeFrame: LF/HF (unit-less value) will be assessed at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
measure: Changes of the index of sympathetic modulation to the vessels (LFSAP) in supine position induced by by feet mechanical stimulation.
timeFrame: LFSAP will be assessed in mmHg2 at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
measure: Changes of plasma Norepinephrine (NE) in supine position induced by feet mechanical stimulation.
timeFrame: Plasma NE will be assessed in ng/L at baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
measure: Changes of plasma Epinephrine (E) in supine position induced by feet mechanical stimulation.
timeFrame: Plasma E will be quantified in ng/L at baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
measure: Changes of Heart Rate (HR beats/min) values during 75°head-up tilt induced by feet mechanical stimulation.
timeFrame: HR will be assessed in beats/min at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
measure: Changes of Blood Pressure (BP) values during 75°head-up tilt induced by feet mechanical stimulation.
timeFrame: BP will be assessed in mmHg at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
measure: Changes of the index of cardiac vagal modulation (HFRR, High Frequency oscillatory component of R-R interval variability at ~0.25Hz) during 75°head-up tilt induced by feet mechanical stimulation.
timeFrame: HFRR will be assessed in (msec2) at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
measure: Changes of the index of cardiac sympathetic modulation (LFRR, Low Frequency oscillatory component of R-R interval variability at ~0.10 Hz) during 75° head-up tilt induced by feet mechanical stimulation.
timeFrame: LFRR will be assessed in msec2 at baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
measure: Changes of the index of cardiac sympatho-vagal modulation (LF/HF)RR during 75°head-up tilt induced by feet mechanical stimulation.
timeFrame: LF/HF (unit-less value) will be assessed at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
measure: Changes of the index of sympathetic modulation to the vessels (LFSAP , mmHg2) during 75°head-up tilt induced by feet mechanical stimulation.
timeFrame: LFSAP will be assessed in mmHg2 at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
measure: Changes of plasma Norepinephrine (NE) during 75°head-up tilt induced by feet mechanical stimulation.
timeFrame: Plasma NE will be quantified in ng/L at baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
measure: Changes of plasmatic Epinephrine (E) during 75°head-up tilt induced by feet mechanical stimulation.
timeFrame: Plasma E will be quantified in ng/L at baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
Secondary outcomes:
measure: Changes in Unified Parkinson's Disease Rating Scale (UDPRS) induced by feet mechanical stimulation.
timeFrame: UDPRS will be done at baseline and 16 days from baseline, after 5 feet mechanical stimulation sessions
measure: Changes in Timed Up and Go induced by feet mechanical stimulation.
timeFrame: Timed Up and Go will be evaluated at Baseline, 72 hours and 16 days from baseline after 5 feet stimulation sessions
Other outcomes:
Locations:
city: Rozzano
country: Italy
facility: Humanitas Research Hospital
Study officials:
affiliation: Humanitas Research Hospital, University of Milan
name: Raffaello Furlan, MD
role: STUDY_DIRECTOR
affiliation: Humanitas Rsearch Hospital, University of Milan
name: Raffaello Furlan, MD
role: STUDY_CHAIR
affiliation: Humanitas Research Hospital; Humanitas University, Rozzano (MI)
name: Franca Barbic, MD
role: PRINCIPAL_INVESTIGATOR
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