Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02608424
Recruitment Status : Completed
First Posted : November 18, 2015
Last Update Posted : August 3, 2018
Sponsor:
Information provided by (Responsible Party):
Istituto Clinico Humanitas

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.

Condition or disease Intervention/treatment Phase
Parkinson's Disease Autonomic Neuropathy Inflammation Hypertension Device: Foot Mechanical Stimulation (Gondola®, CE marking n° 0476) Not Applicable

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Effects of Feet Mechanical Stimulation on the Inflammatory State and Cardiovascular Autonomic Profile in Patients With Parkinson's Disease
Actual Study Start Date : March 2015
Actual Primary Completion Date : August 2016
Actual Study Completion Date : August 2017

Resource links provided by the National Library of Medicine


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 Name: Pressure-controlled mechanical stimulator (Gondola®)




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.


Secondary Outcome Measures :
  1. 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

  2. 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)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   50 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02608424


Locations
Layout table for location information
Italy
Humanitas Research Hospital
Rozzano, Italy, 20089
Sponsors and Collaborators
Istituto Clinico Humanitas
Investigators
Layout table for investigator information
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:

Layout table for additonal information
Responsible Party: Istituto Clinico Humanitas
ClinicalTrials.gov Identifier: NCT02608424    
Other Study ID Numbers: parkgo-1-ICH
First Posted: November 18, 2015    Key Record Dates
Last Update Posted: August 3, 2018
Last Verified: August 2018
Keywords provided by Istituto Clinico Humanitas:
Foot mechanical stimulation
Autonomic nervous system
Inflammation
Parkinson's disease
Spectral analysis
Heart rate variability
Blood pressure variability
Additional relevant MeSH terms:
Layout table for MeSH terms
Parkinson Disease
Inflammation
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Pathologic Processes