The Effects of Ischemic Conditioning in Individuals with Parkinson's Disease

October 16, 2024 updated by: Hospital Israelita Albert Einstein

The Chronic Effect of Ischemic Conditioning on Motor Function, Cognitive Performance, and Immune System in Individuals with Parkinson's Disease

Ischemic conditioning (IC) is a promising therapy that can mimic the physiological effects of physical exercise. IC consists of using a cuff to measure blood pressure and calibrate 200 mmHg on the upper or lower limb. Thus, at alternating intervals of 5 minutes, ischemia or reperfusion occurs, depending on whether the cuff is inflated or deflated. IC induces changes in spinal cord excitability for the last reflex reactions of recruited motoneurons with improved balance control in healthy young people and improved learning in the elderly. The objective of the present study is to evaluate the chronic effect of IC on the motor function and cognitive performance of patients with Parkinson's disease. Furthermore, the investigators will evaluate secondary outcomes such as mobility, quality of life, and immunological responses.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Parkinson's disease (PD) is a neurodegenerative disorder that causes a variety of motor and non-motor symptoms. Typically, patients with PD suffer from disabilities and secondary complications even when the disease is optimally treated, and many patients still have sedentary lifestyles, which in turn result in higher rates of mortality and comorbidity. Physical activity is an essential element in maintaining daily functional capabilities and quality of life. However, patients with PD have motor and non-motor deficits that can prevent or limit physical exercise, such as running or resistance exercise. Ischemic conditioning (IC) is a promising therapy that can mimic the physiological effects of physical exercise. IC consists of using a cuff to measure blood pressure, calibrated between 180 and 200 mmHg on the upper or lower limb. Thus, at alternating intervals of 5 minutes, ischemia or reperfusion occurs, depending on whether the cuff is inflated or deflated. IC induces changes in spinal cord excitability for the last reflex reactions of recruited motoneurons with improved balance control in healthy young people and improved learning in the elderly. Recently, IC has been shown to improve cognitive performance in neurological patients with stroke, subcortical ischemia, and vascular dementia. However, there are no studies that have evaluated the effect of IC on motor and cognitive performance in patients with PD. The objective of the present study is to evaluate the chronic effect of IC on the motor and cognitive performance of patients with PD. Furthermore, the investigators intend to evaluate other secondary outcomes such as mobility, quality of life, and immunological responses.

Study Type

Interventional

Enrollment (Estimated)

34

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 Contact

Study Contact Backup

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • PD patients aged 40 years or older;
  • Diagnosis of PD without cognitive complaints or with complaints, but without impact on daily activities;

Exclusion Criteria:

  • Patients with uncontrolled diabetes mellitus or peripheral neuropathy;
  • Uncontrolled arterial hypertension (BP>160/100mmHg);
  • Uncontrolled diabetes (Fasting glucose > 250mg/dl, peripheral retinopathy or diabetic ketoacidosis);
  • Uncontrolled dyslipidemia (total chol > 220mg/dL);
  • Pre-existing autoimmune diseases;
  • Infectious conditions for less than 1 month;
  • Neurological problems that prevent training from being carried out;
  • History of anemia, cerebral vascular disease, myocardial infarction in the last 6 months;
  • Previous deep vein thrombosis;
  • Smoking < 6 months;
  • Symptomatic peripheral arterial obstructive disease;
  • Cognitive dysfunction: Moca < 24.

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: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ischemic conditioning group
Therapy will be performed bilaterally on the upper limbs. The ischemic conditioning group will perform 4 times, 8 cycles with 30 seconds of ischemia (80 - 200 mmHg) with 5 seconds of reperfusion in each cycle. Ischemia cycles are controlled by a device (KAATSU C3 - KAATSU GLOBAL / USA) In the first cycle, participants will be subjected to pressures of 80 to 150 mmHg. In the 3 subsequent cycles, pressures from 130 to 200 mmHg will be applied.
Device: Ischemic conditioning group
The ischemic conditioning protocol will consist of a period of 12 weeks (24 sessions) with a frequency of 2 weekly sessions lasting between 15 and 20 minutes each. Therapy will be performed bilaterally on the upper limbs. The ischemic conditioning group will perform 4 times, 8 cycles with 30 seconds of ischemia (80 - 200 mmHg) with 5 seconds of reperfusion in each cycle. Ischemia cycles are controlled by a device (KAATSU C3 - KAATSU GLOBAL / USA) with customized ischemia programs, partially restricting blood flow through special pressure cuffs that are internally valved, providing greater comfort and safety for these patients who typically have stiffness in the affected limb and localized muscle pain. In the first cycle, participants will be subjected to pressures of 80 to 150 mmHg. In the 3 subsequent cycles, pressures from 130 to 200 mmHg will be applied.
Sham Comparator: Sham group
Participants in the control group (Sham) will perform 4 cycles of 5 minutes of ischemia (30 mmHg) with 4 subsequent cycles of reperfusion (rest) bilaterally in the arms with a sphygmomanometer (Welch Allyn DS44-11BR Durashock).
Device: Sham group
Participants in the control group (Sham) will perform 4 cycles of 5 minutes of ischemia (30 mmHg) with 4 subsequent cycles of reperfusion (rest) bilaterally in the arms with a sphygmomanometer

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Unified Parkinson's Disease Rating Scale
Time Frame: Before intervention and at week 12
0-260 points: A higher score indicates greater impairment
Before intervention and at week 12
Montreal cognitive assesment
Time Frame: Before intervention and at week 12
Maximum score: 30 points; Normal cognition: 26-30 points; Mild cognitive impairment (MCI): Below 26 points
Before intervention and at week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessment of cellular and soluble immune response
Time Frame: Before intervention and at week 12
The patient's peripheral blood will be collected in three EDTA tubes of 5 mL each before and after 12 weeks of application of the ischemic conditioning protocol. From the blood samples, plasma will be obtained for quantification of soluble mediators, followed by the isolation/storage of peripheral blood mononuclear cells (PBMC or Peripheral Blood Mononuclear Cell) for phenotypic characterization of subpopulations of T and B lymphocytes, NK cells, myeloids and monocytes
Before intervention and at week 12
Quantifications of systemic soluble mediators
Time Frame: Before intervention and at week 12
Initially, the EDTA tubes containing the blood will be centrifuged for 5 minutes at 400 x g and 20 ºC to separate the plasma. The collected plasma will be aliquoted into cryotubes and stored at -80ºC until the tests are carried out. Quantification of systemic soluble mediators will be performed using the MILLIPLEX® Human Cytokine/Chemokine/Growth Factor Panel A Kit H - Immunology Multiplex Assay (Merck Millipore, Massachusetts, USA). The panel of analytes included chemokines, growth factors, pro-inflammatory cytokines and regulatory cytokines: FGF-2/FGF-basic, G-CSF, GM-CSF, IFNa2,IFNy, IL-1a, IL-1b, IL-1RA , IL-2, IL-4, IL-6, IL-7, IL-8/CXCL8, IL-10, IL-12 (p40), IL-12 (p70), IL-13, IL-15, IL -17A/CTLA8, IL-18, IP-10/CXCL10, MCP-1/CCL2, MCP-3/CCL7, M-CSF, MIG/CXCL9, MIP-1a/CCL3, MIP-1b/CCL4, PDGF-AB /BB, RANTES/CCL5, TNFa, TNFb/Lymphotoxin-a, VEGF-A, HIF-1ą. The PCR, BNDF, and Irisin proteins will be measured using single-plex assays.
Before intervention and at week 12
PBMC acquisition and flow cytometry
Time Frame: Before intervention and at week 12
Finally, a minimum of 100,000 events will be acquired on the BD LSRFortessa™ flow cytometer (BD Biosciences).
Before intervention and at week 12
The Parkinson's Disease Questionnaire-39
Time Frame: Before intervention and at week 12
The overall score ranges from 0 to 100%, with higher scores indicating a greater negative impact of Parkinson's Disease on the patient's quality of life.
Before intervention and at week 12
Timed up and go
Time Frame: Before intervention and at week 12

<10 seconds: Individuals are generally able to perform most daily activities independently without assistance; 10-19 seconds: Indicates independence in most daily activities but may suggest slight mobility limitations; 20-29 seconds: Suggests the need for assistance with mobility, especially for more challenging tasks;

≥30 seconds: Indicates a high fall risk, and the individual likely needs assistance with many daily tasks and may require mobility aids.
Before intervention and at week 12

Collaborators and Investigators

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

Sponsor

Hospital Israelita Albert Einstein

Collaborators

Unifesp Escola Paulista de Medicina

Investigators

  • Principal Investigator: Kenneth Gollob, PhD, Hospital Israelita Albert Einstein

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 (Estimated)

March 1, 2025

Primary Completion (Estimated)

August 1, 2027

Study Completion (Estimated)

September 1, 2027

Study Registration Dates

First Submitted

February 19, 2024

First Submitted That Met QC Criteria

February 27, 2024

First Posted (Actual)

March 5, 2024

Study Record Updates

Last Update Posted (Actual)

October 18, 2024

Last Update Submitted That Met QC Criteria

October 16, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 71055423.3.0000.0071

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

Yes

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.

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