Effects of Feet Mechanical Stimulation on Cardiovascular Autonomic Profile and Inflammation in Parkinson's Disease (parkgo-1)

August 1, 2018 updated by: Istituto Clinico Humanitas

Effects of Feet Mechanical Stimulation on the Inflammatory State and Cardiovascular Autonomic Profile in Patients With Parkinson's Disease

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Rozzano, Italy, 20089
        • Humanitas Research Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Foot Mechanical Stimulation

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)
The feet mechanical stimulation will be performed by Gondola (Gondola®, CE marking n° 0476).
Other Names:
  • Pressure-controlled mechanical stimulator (Gondola®)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes of Pentraxin 3 (PTX3) plasma levels induced by feet mechanical stimulation.
Time Frame: Blood samples will be collected at Baseline, and 16 days from baseline (after 5 feet mechanical stimulation sessions).
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.
Time Frame: Blood samples will be collected at Baseline, and 16 days from baseline (after 5 feet mechanical stimulation sessions).
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.
Time Frame: Blood samples will be collected at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
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.
Time Frame: Blood samples will be collected at Baseline, and 16 days from baseline (after 5 feet mechanical stimulation sessions).
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.
Time Frame: HR will be assessed in beats/min at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
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.
Time Frame: BP will be assessed in mmHg at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
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.
Time Frame: HFRR will be assessed in msec2 at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
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.
Time Frame: LFRR will be assessed in msec2 at baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
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.
Time Frame: LF/HF (unit-less value) will be assessed at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
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.
Time Frame: LFSAP will be assessed in mmHg2 at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
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.
Time Frame: Plasma NE will be assessed in ng/L at baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
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.
Time Frame: Plasma E will be quantified in ng/L at baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
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.
Time Frame: HR will be assessed in beats/min at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
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.
Time Frame: BP will be assessed in mmHg at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
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.
Time Frame: HFRR will be assessed in (msec2) at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
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.
Time Frame: LFRR will be assessed in msec2 at baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
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.
Time Frame: LF/HF (unit-less value) will be assessed at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
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.
Time Frame: LFSAP will be assessed in mmHg2 at Baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
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.
Time Frame: Plasma NE will be quantified in ng/L at baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
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.
Time Frame: Plasma E will be quantified in ng/L at baseline and 16 days from baseline (after 5 feet mechanical stimulation sessions).
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in Unified Parkinson's Disease Rating Scale (UDPRS) induced by feet mechanical stimulation.
Time Frame: UDPRS will be done at baseline and 16 days from baseline, after 5 feet mechanical stimulation sessions
UDPRS will be performed by neurologist
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.
Time Frame: Timed Up and Go will be evaluated at Baseline, 72 hours and 16 days from baseline after 5 feet stimulation sessions
Timed Up and Go test will be performed before and after the feet mechanical stimulations at baseline,72 hours and 16 days from baseline (i.e. after 5 stimulations)
Timed Up and Go will be evaluated at Baseline, 72 hours and 16 days from baseline after 5 feet stimulation sessions

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Istituto Clinico Humanitas

Investigators

  • Study Director: Raffaello Furlan, MD, Humanitas Research Hospital, University of Milan
  • Study Chair: Raffaello Furlan, MD, Humanitas Rsearch Hospital, University of Milan
  • Principal Investigator: Franca Barbic, MD, Humanitas Research Hospital; Humanitas University, Rozzano (MI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2015

Primary Completion (Actual)

August 1, 2016

Study Completion (Actual)

August 1, 2017

Study Registration Dates

First Submitted

October 27, 2015

First Submitted That Met QC Criteria

November 16, 2015

First Posted (Estimate)

November 18, 2015

Study Record Updates

Last Update Posted (Actual)

August 3, 2018

Last Update Submitted That Met QC Criteria

August 1, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • parkgo-1-ICH

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Inflammation

Clinical Trials on Foot Mechanical Stimulation (Gondola®, CE marking n° 0476)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in New Zealand

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe