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

Hypertension Clinical Trial

— parkgo-1  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02608424
• Other study ID #: parkgo-1-ICH
• Status: Completed
• Phase: N/A
• Start date: March 2015
• Est. completion date: August 2017

Study information

• Verified date: August 2018
• Source: Istituto Clinico Humanitas
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: August 2017
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Autonomic Neuropathy
• Hypertension
• Inflammation
• Parkinson Disease
• Parkinson's Disease

Intervention

Device:
• Foot Mechanical Stimulation (Gondola®, CE marking n° 0476)
The feet mechanical stimulation will be performed by Gondola (Gondola®, CE marking n° 0476).

Locations

Country	Name	City	State
Italy	Humanitas Research Hospital	Rozzano

Sponsors (1)

Lead Sponsor	Collaborator
Istituto Clinico Humanitas

Country where clinical trial is conducted

Italy, 

References & Publications (21)

Allcock LM, Ullyart K, Kenny RA, Burn DJ. Frequency of orthostatic hypotension in a community based cohort of patients with Parkinson's disease. J Neurol Neurosurg Psychiatry. 2004 Oct;75(10):1470-1. — View Citation

Barbic F, Galli M, Dalla Vecchia L, Canesi M, Cimolin V, Porta A, Bari V, Cerri G, Dipaola F, Bassani T, Cozzolino D, Pezzoli G, Furlan R. Effects of mechanical stimulation of the feet on gait and cardiovascular autonomic control in Parkinson's disease. J Appl Physiol (1985). 2014 Mar 1;116(5):495-503. doi: 10.1152/japplphysiol.01160.2013. Epub 2014 Jan 16. — View Citation

Barbic F, Perego F, Canesi M, Gianni M, Biagiotti S, Costantino G, Pezzoli G, Porta A, Malliani A, Furlan R. Early abnormalities of vascular and cardiac autonomic control in Parkinson's disease without orthostatic hypotension. Hypertension. 2007 Jan;49(1):120-6. Epub 2006 Nov 13. — View Citation

Bernardi L, Bissa M, DeBarbieri G, Bharadwaj A, Nicotra A. Arterial baroreflex modulation influences postural sway. Clin Auton Res. 2011 Jun;21(3):151-60. doi: 10.1007/s10286-010-0099-x. Epub 2010 Dec 24. — View Citation

Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad N, Eaton JW, Tracey KJ. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature. 2000 May 25;405(6785):458-62. — View Citation

Bottazzi B, Doni A, Garlanda C, Mantovani A. An integrated view of humoral innate immunity: pentraxins as a paradigm. Annu Rev Immunol. 2010;28:157-83. doi: 10.1146/annurev-immunol-030409-101305. Review. — View Citation

de Lau LM, Breteler MM. Epidemiology of Parkinson's disease. Lancet Neurol. 2006 Jun;5(6):525-35. Review. — View Citation

Emre M. Dementia associated with Parkinson's disease. Lancet Neurol. 2003 Apr;2(4):229-37. Review. — View Citation

Findley LJ. The economic impact of Parkinson's disease. Parkinsonism Relat Disord. 2007 Sep;13 Suppl:S8-S12. Epub 2007 Aug 16. Review. — View Citation

Furlan R, Ardizzone S, Palazzolo L, Rimoldi A, Perego F, Barbic F, Bevilacqua M, Vago L, Bianchi Porro G, Malliani A. Sympathetic overactivity in active ulcerative colitis: effects of clonidine. Am J Physiol Regul Integr Comp Physiol. 2006 Jan;290(1):R224-32. Epub 2005 Aug 25. — View Citation

Furlan R, Porta A, Costa F, Tank J, Baker L, Schiavi R, Robertson D, Malliani A, Mosqueda-Garcia R. Oscillatory patterns in sympathetic neural discharge and cardiovascular variables during orthostatic stimulus. Circulation. 2000 Feb 29;101(8):886-92. — View Citation

Gademan MG, Sun Y, Han L, Valk VJ, Schalij MJ, van Exel HJ, Lucas CM, Maan AC, Verwey HF, van de Vooren H, Pinna GD, Maestri R, La Rovere MT, van der Wall EE, Swenne CA. Rehabilitation: Periodic somatosensory stimulation increases arterial baroreflex sensitivity in chronic heart failure patients. Int J Cardiol. 2011 Oct 20;152(2):237-41. doi: 10.1016/j.ijcard.2010.07.022. Epub 2010 Aug 9. — View Citation

Garlanda C, Bottazzi B, Bastone A, Mantovani A. Pentraxins at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility. Annu Rev Immunol. 2005;23:337-66. Review. — View Citation

Huse DM, Schulman K, Orsini L, Castelli-Haley J, Kennedy S, Lenhart G. Burden of illness in Parkinson's disease. Mov Disord. 2005 Nov;20(11):1449-54. — View Citation

Lee HW, Choi J, Suk K. Increases of pentraxin 3 plasma levels in patients with Parkinson's disease. Mov Disord. 2011 Nov;26(13):2364-70. doi: 10.1002/mds.23871. Epub 2011 Sep 23. — View Citation

Lee JK, Tran T, Tansey MG. Neuroinflammation in Parkinson's disease. J Neuroimmune Pharmacol. 2009 Dec;4(4):419-29. doi: 10.1007/s11481-009-9176-0. Epub 2009 Oct 10. Review. — View Citation

Mantovani A, Garlanda C, Doni A, Bottazzi B. Pentraxins in innate immunity: from C-reactive protein to the long pentraxin PTX3. J Clin Immunol. 2008 Jan;28(1):1-13. Epub 2007 Sep 9. Review. — View Citation

Porta A, Castiglioni P, Di Rienzo M, Bari V, Bassani T, Marchi A, Takahashi AC, Tobaldini E, Montano N, Catai AM, Barbic F, Furlan R, Cividjian A, Quintin L. Short-term complexity indexes of heart period and systolic arterial pressure variabilities provide complementary information. J Appl Physiol (1985). 2012 Dec 15;113(12):1810-20. doi: 10.1152/japplphysiol.00755.2012. Epub 2012 Oct 25. — View Citation

Prätorius B, Kimmeskamp S, Milani TL. The sensitivity of the sole of the foot in patients with Morbus Parkinson. Neurosci Lett. 2003 Aug 7;346(3):173-6. — View Citation

Schmidt C, Berg D; Herting, Prieur S, Junghanns S, Schweitzer K, Globas C, Schöls L, Reichmann H, Ziemssen T. Loss of nocturnal blood pressure fall in various extrapyramidal syndromes. Mov Disord. 2009 Oct 30;24(14):2136-42. doi: 10.1002/mds.22767. — View Citation

Sharabi Y, Goldstein DS. Mechanisms of orthostatic hypotension and supine hypertension in Parkinson disease. J Neurol Sci. 2011 Nov 15;310(1-2):123-8. doi: 10.1016/j.jns.2011.06.047. Epub 2011 Jul 16. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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	Changes in Unified Parkinson's Disease Rating Scale (UDPRS) induced by feet mechanical stimulation.	UDPRS will be performed by neurologist	UDPRS will be done at baseline and 16 days from baseline, after 5 feet mechanical stimulation sessions
Secondary	Changes in Timed Up and Go induced by feet mechanical stimulation.	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