Effects of Feet Mechanical Stimulation on Cardiovascular Autonomic Profile and Inflammation in Parkinson's Disease

NCT02608424 | Completed

• 1 other identifier: parkgo-1-ICH
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (20)

• Changes of Pentraxin 3 (PTX3) plasma levels induced by feet mechanical stimulation.

  PTX3 as an index of systemic inflammatory profile will be assessed by a developed and optimized ELISA and expressed by ng/ml.

  Blood samples will be collected at Baseline, and 16 days from baseline (after 5 feet mechanical stimulation sessions).

• Changes of Interleukine-6 (IL-6), plasma levels induced by feet mechanical stimulation.

  IL-6 will be tested by commercially available ELISA and immunoturbidimetric assays and expressed by ng/ml.

  Blood samples will be collected at Baseline, and 16 days from baseline (after 5 feet mechanical stimulation sessions).

• Changes of Tumor Necrosis Factor (TNF) plasma levels induced by feet mechanical stimulation.

  TNF will be tested by commercially available ELISA and immunoturbidimetric assays and expressed by ng/ml.

  Blood samples will be collected at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).

• Changes of C Reactive Protein (CRP) plasma levels induced by feet mechanical stimulation.

  CRP will be tested by commercially available ELISA and immunoturbidimetric assays and expressed by mg/dl.

  Blood samples will be collected at Baseline, and 16 days from baseline (after 5 feet mechanical stimulation sessions).

• Changes of Heart Rate (HR) values in supine position induced by feet mechanical stimulation.

  Mean value of 15 minute-ECG continuous recording in supine position will be used.

  HR will be assessed in beats/min at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).

• Changes of Blood Pressure (BP) values in supine position induced by feet mechanical stimulation.

  Mean value of 5 measures obtained every 3 minutes by an Automatic-cycling non-invasive blood pressure monitor in supine position will be used.

  BP will be assessed in mmHg at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).

• 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.

  HFRR will be obtained by the spectral analysis of R-R interval spontaneous variability in supine position.

  HFRR will be assessed in msec2 at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).

• 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.

  LFRR will be obtained by the spectral analysis of R-R interval spontaneous variability in supine position.

  LFRR will be assessed in msec2 at baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).

• Changes of the index of cardiac sympatho-vagal modulation (LF/HF)RR in supine position induced by feet mechanical stimulation.

  LF/HF is the ratio between LFRR index of cardiac sympathetic modulation and HFRR index of the cardiac vagal modulation obtained by the spectral analysis of R-R interval spontaneous variability.

  LF/HF (unit-less value) will be assessed at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).

• Changes of the index of sympathetic modulation to the vessels (LFSAP) in supine position induced by by feet mechanical stimulation.

  LFSAP will be quantified by spectral analysis of systolic arterial pressure variability obtained by beat by beat blood pressure non-invasive continuous recording in supine position.

  LFSAP will be assessed in mmHg2 at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).

• Changes of plasma Norepinephrine (NE) in supine position induced by feet mechanical stimulation.

  Plasma NE will be quantified by High Performance Liquid Chromatography (HPLC) with electrochemical detection (ED) from blood samples collected in supine position

  Plasma NE will be assessed in ng/L at baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).

• Changes of plasma Epinephrine (E) in supine position induced by feet mechanical stimulation.

  Plasma E will be quantified by High Performance Liquid Chromatography (HPLC) and electrochemical detection (ED) from blood samples collected in supine position

  Plasma E will be quantified in ng/L at baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).

• Changes of Heart Rate (HR beats/min) values during 75°head-up tilt induced by feet mechanical stimulation.

  The mean value of 15 minute-ECG continuous recording during 75°head-up tilt will be used.

  HR will be assessed in beats/min at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).

• Changes of Blood Pressure (BP) values during 75°head-up tilt induced by feet mechanical stimulation.

  The mean value of 5 measures obtained every 3 minutes by an automatic-cycling non-invasive blood pressure monitor during 75°head-up tilt will be used.

  BP will be assessed in mmHg at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).

• 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.

  HFRR will be obtained by the spectral analysis of R-R interval spontaneous variability during 75°head-up tilt.

  HFRR will be assessed in (msec2) at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).

• 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.

  LFRR will be obtained by the spectral analysis of R-R interval spontaneous variability during 75° head-up tilt.

  LFRR will be assessed in msec2 at baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).

• Changes of the index of cardiac sympatho-vagal modulation (LF/HF)RR during 75°head-up tilt induced by feet mechanical stimulation.

  LF/HF will be quantified as a ratio between LFRR index of cardiac sympathetic modulation and HFRR index of the cardiac vagal modulation obtained by the spectral analysis of R-R interval spontaneous variability during 75°head-up tilt.

  LF/HF (unit-less value) will be assessed at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).

• Changes of the index of sympathetic modulation to the vessels (LFSAP , mmHg2) during 75°head-up tilt induced by feet mechanical stimulation.

  LFSAP expressed will be quantified by spectral analysis of systolic arterial pressure variability obtained by beat by beat blood pressure non-invasive continuous recording during 75°head-up tilt.

  LFSAP will be assessed in mmHg2 at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).

• Changes of plasma Norepinephrine (NE) during 75°head-up tilt induced by feet mechanical stimulation.

  Plasma NE will be evaluated by High Performance Liquid Chromatography (HPLC) with electrochemical detection (ED) from blood samples collected after 5 minutes of 75°head-up tilt.

  Plasma NE will be quantified in ng/L at baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).

• Changes of plasmatic Epinephrine (E) during 75°head-up tilt induced by feet mechanical stimulation.

  Plasma E will be evaluated by High Performance Liquid Chromatography (HPLC) and electrochemical detection (ED) from blood samples collected after 5 minutes lasting 75°head-up tilt.

  Plasma E will be quantified in ng/L at baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).

Secondary Outcomes (2)

• Changes in Unified Parkinson's Disease Rating Scale (UDPRS) induced by feet mechanical stimulation.

  UDPRS will be done at baseline and 16 days from baseline, after 5 feet mechanical stimulation sessions

• Changes in Timed Up and Go induced by feet mechanical stimulation.

  Timed Up and Go will be evaluated at Baseline, 72 hours and 16 days from baseline after 5 feet stimulation sessions

Study Arms (1)

Foot Mechanical Stimulation

EXPERIMENTAL

Intervention: Foot Mechanical Stimulation (FMS) will be performed on enrolled patients every 72 hours (total 5 stimulation sessions) by a pressure-controlled mechanical stimulator (Gondola®, European Community (CE) marking n° 0476) . The sites of the stimulation will be the tip of the hallux and the lower big toe first metatarsal joint plantar surface. The FMS procedure consists in the application of the patient's calibrated pressure for 6 seconds, over the selected sites. Each of the 2 cutaneous sites of both feet will be mechanically stimulated. The procedure will be automatically repeated for 4 times in every subject so that the overall time of stimulation will be approximately 2 minutes.

Device: Foot Mechanical Stimulation (Gondola®, CE marking n° 0476)

Interventions

Foot Mechanical Stimulation (Gondola®, CE marking n° 0476) DEVICE

The feet mechanical stimulation will be performed by Gondola (Gondola®, CE marking n° 0476).

Also known as: Pressure-controlled mechanical stimulator (Gondola®)

Foot Mechanical Stimulation

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Istituto Clinico Humanitas: lead

Study Sites (1)

Humanitas Research Hospital

Rozzano, 20089, Italy

Location

Related Publications (21)

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MeSH Terms

Conditions

Parkinson Disease; Inflammation; Hypertension

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Raffaello Furlan, MD

  Humanitas Research Hospital, University of Milan

  STUDY DIRECTOR

• Raffaello Furlan, MD

  Humanitas Rsearch Hospital, University of Milan

  STUDY CHAIR

• Franca Barbic, MD

  Humanitas Research Hospital; Humanitas University, Rozzano (MI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2015
• First Posted: November 18, 2015
• Study Start: March 1, 2015
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2017
• Last Updated: August 3, 2018

Record last verified: 2018-08

Locations

IT (1)