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

NCT06293118 | Not Yet Recruiting DMC FDA Device

• 1 other identifier: 71055423.3.0000.0071
• Study Type: interventional
• Target: 34
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Parkinson Disease

Keywords

ischemic conditioning; immune system; motor function; cognitive performance; Parkinson disease

Outcome Measures

Primary Outcomes (2)

• Unified Parkinson's Disease Rating Scale

  0-260 points: A higher score indicates greater impairment

  Before intervention and at week 12

• Montreal cognitive assesment

  Maximum score: 30 points; Normal cognition: 26-30 points; Mild cognitive impairment (MCI): Below 26 points

  Before intervention and at week 12

Secondary Outcomes (5)

• The Parkinson's Disease Questionnaire-39

  Before intervention and at week 12

• Timed up and go

  Before intervention and at week 12

• Assessment of cellular and soluble immune response

  Before intervention and at week 12

• Quantifications of systemic soluble mediators

  Before intervention and at week 12

• PBMC acquisition and flow cytometry

  Before intervention and at week 12

Study Arms (2)

Ischemic conditioning group

EXPERIMENTAL

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

Sham group

SHAM COMPARATOR

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

Interventions

Ischemic conditioning group DEVICE

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.

Ischemic conditioning group

Sham group DEVICE

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

Sham group

Eligibility Criteria

• Age: 40 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospital Israelita Albert Einstein: lead
• Unifesp Escola Paulista de Medicina: collaborator

Related Publications (17)

• Poewe et al. Parkinson disease. Nat Rev 2017;3:1-21. doi:10.1038/nrdp.2017.13

  BACKGROUND

• 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 BACKGROUND

• Kaushik S, Cuervo AM. Proteostasis and aging. Nat Med. 2015 Dec;21(12):1406-15. doi: 10.1038/nm.4001.

  PMID: 26646497 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Xu R, He Q, Wang Y, Yang Y, Guo ZN. Therapeutic Potential of Remote Ischemic Conditioning in Vascular Cognitive Impairment. Front Cell Neurosci. 2021 Aug 3;15:706759. doi: 10.3389/fncel.2021.706759. eCollection 2021.

  PMID: 34413726 BACKGROUND

• Loukogeorgakis SP, Williams R, Panagiotidou AT, Kolvekar SK, Donald A, Cole TJ, Yellon DM, Deanfield JE, MacAllister RJ. Transient limb ischemia induces remote preconditioning and remote postconditioning in humans by a K(ATP)-channel dependent mechanism. Circulation. 2007 Sep 18;116(12):1386-95. doi: 10.1161/CIRCULATIONAHA.106.653782. Epub 2007 Aug 27.

  PMID: 17724264 BACKGROUND

• Strijdom H, Friedrich SO, Hattingh S, Chamane N, Lochner A. Hypoxia-induced regulation of nitric oxide synthase in cardiac endothelial cells and myocytes and the role of the PI3-K/PKB pathway. Mol Cell Biochem. 2009 Jan;321(1-2):23-35. doi: 10.1007/s11010-008-9906-2. Epub 2008 Sep 14.

  PMID: 18791856 BACKGROUND

• Sutter EN, Mattlage AE, Bland MD, Cherry-Allen KM, Harrison E, Surkar SM, Gidday JM, Chen L, Hershey T, Lee JM, Lang CE. Remote Limb Ischemic Conditioning and Motor Learning: Evaluation of Factors Influencing Response in Older Adults. Transl Stroke Res. 2019 Aug;10(4):362-371. doi: 10.1007/s12975-018-0653-8. Epub 2018 Aug 7.

  PMID: 30088217 BACKGROUND

• Guo ZN, Guo WT, Liu J, Chang J, Ma H, Zhang P, Zhang FL, Han K, Hu HH, Jin H, Sun X, Simpson DM, Yang Y. Changes in cerebral autoregulation and blood biomarkers after remote ischemic preconditioning. Neurology. 2019 Jul 2;93(1):e8-e19. doi: 10.1212/WNL.0000000000007732. Epub 2019 May 29.

  PMID: 31142636 BACKGROUND

• He Z, Xu N, Qi S. Remote ischemic preconditioning improves the cognitive function of elderly patients following colon surgery: A randomized clinical trial. Medicine (Baltimore). 2017 Apr;96(17):e6719. doi: 10.1097/MD.0000000000006719.

  PMID: 28445286 BACKGROUND

• Zhou D, Ding J, Ya J, Pan L, Bai C, Guan J, Wang Z, Jin K, Yang Q, Ji X, Meng R. Efficacy of remote ischemic conditioning on improving WMHs and cognition in very elderly patients with intracranial atherosclerotic stenosis. Aging (Albany NY). 2019 Jan 28;11(2):634-648. doi: 10.18632/aging.101764.

  PMID: 30689549 BACKGROUND

• Liao Z, Bu Y, Li M, Han R, Zhang N, Hao J, Jiang W. Remote ischemic conditioning improves cognition in patients with subcortical ischemic vascular dementia. BMC Neurol. 2019 Aug 23;19(1):206. doi: 10.1186/s12883-019-1435-y.

  PMID: 31443692 BACKGROUND

• Movement Disorder Society Task Force on Rating Scales for Parkinson's Disease. The Unified Parkinson's Disease Rating Scale (UPDRS): status and recommendations. Mov Disord. 2003 Jul;18(7):738-50. doi: 10.1002/mds.10473.

  PMID: 12815652 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Kenneth Gollob, PhD

  Hospital Israelita Albert Einstein

  PRINCIPAL INVESTIGATOR

Central Study Contacts

SAMUEL AMORIM DE SOUZA, Master

CONTACT

11983331912; samuel.amorim.s@gmail.com

Kenneth J Gollob, PhD

CONTACT

31 996719224; kjgollob.einstein@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Patients were unaware of the allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 1. Ischemic conditioning group 2. control group (Sham)

Study Record Dates

• First Submitted: February 19, 2024
• First Posted: March 5, 2024
• Study Start: March 1, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: October 18, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share