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

Official title

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

Overview

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.

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.

Interventions

• 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 C4 - KAATSU GLOBAL / USA) with customized ischemia programs, partially rest
• Device Sham group
  In the sham group, participants will complete the same number of sets (4) and 4 cycles, with equalized time to ischemia (4 minutes) and (40 seconds) reperfusion timing, but at a non-occlusive pressure of 30 mmHg. Device, cuff placement, instructions, staff contact, and session duration will be standardized across groups.

Primary outcome measures

• Unified Parkinson's Disease Rating Scale [Time frame: Before intervention and at week 12]
• Montreal cognitive assesment [Time frame: Before intervention and at week 12]

Secondary outcome measures (5)

• The Parkinson's Disease Questionnaire-39 [Time frame: Before intervention and at week 12]
• Timed up and go [Time frame: Before intervention and at week 12]
• Assessment of cellular and soluble immune response [Time frame: Before intervention and at week 12]
• Quantifications of systemic soluble mediators [Time frame: Before intervention and at week 12]
• PBMC acquisition and flow cytometry [Time frame: Before intervention and at week 12]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Poewe et al. Parkinson disease. Nat Rev 2017;3:1-21. doi:10.1038/nrdp.2017.13
• Dickson DW, Braak H, Duda JE, Duyckaerts C, Gasser T, Halliday GM, Hardy J, Leverenz JB, Del Tredici K, Wszolek ZK, Litvan I. Neuropathological assessment of Parkinson's disease: refining the diagnostic criteria. Lancet Neurol. 2009 Dec;8(12):1150-7. doi: 10.1016/S1474-4422(09)70238-8. PMID 19909913
• Kaushik S, Cuervo AM. Proteostasis and aging. Nat Med. 2015 Dec;21(12):1406-15. doi: 10.1038/nm.4001. PMID 26646497
• Bose A, Beal MF. Mitochondrial dysfunction in Parkinson's disease. J Neurochem. 2016 Oct;139 Suppl 1:216-231. doi: 10.1111/jnc.13731. Epub 2016 Aug 21. PMID 27546335
• Poewe W. Clinical measures of progression in Parkinson's disease. Mov Disord. 2009;24 Suppl 2:S671-6. doi: 10.1002/mds.22600. PMID 19877235
• Post B, Merkus MP, de Bie RM, de Haan RJ, Speelman JD. Unified Parkinson's disease rating scale motor examination: are ratings of nurses, residents in neurology, and movement disorders specialists interchangeable? Mov Disord. 2005 Dec;20(12):1577-84. doi: 10.1002/mds.20640. PMID 16116612
• Schapira AHV, Chaudhuri KR, Jenner P. Non-motor features of Parkinson disease. Nat Rev Neurosci. 2017 Jul;18(7):435-450. doi: 10.1038/nrn.2017.62. Epub 2017 Jun 8. PMID 28592904
• Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. doi: 10.1111/j.1532-5415.2005.53221.x. PMID 15817019

Identifiers

NCT: NCT06293118 · 71055423.3.0000.0071

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗