The Effect of Spinal Cord Stimulation on Orthostatic Hypotension in Parkinsonism and Its Related Mechanisms

Overview

Parkinson's disease (PDS) is a syndrome characterized by tremor, bradykinesia, rigidity, and postural disturbances. Causes include Parkinson's disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). Non-motor symptoms of PDS, such as neurogenic orthostatic hypotension (nOH), have received more intensive research due to their greater disabling potential compared to motor symptoms. In patients with PD and MSA, nOH can lead to intolerance to medications such as levodopa, significantly increasing the risk of falls, accelerating cognitive decline, and increasing the risk of all-cause mortality. However, conventional pharmacological treatments (such as midodrine, droxidopa, and fludrocortisone) and non-pharmacological approaches (such as compression abdominal bands, elastic stockings, and deep brain stimulation) for non-motor symptoms such as nOH have numerous limitations, including short-term efficacy, uncertain efficacy, and side effects. Therefore, exploring new non-pharmacological treatments to improve nOH and delay disease progression in patients with PDS is crucial for improving their quality of life and prognosis. Spinal cord stimulation (SCS), including invasive (epidural) spinal cord stimulation (eSCS) and non-invasive (transcutaneous) spinal cord stimulation (tSCS), is a novel neuromodulatory technique with clinical applications in a variety of neurological diseases. Currently, several small-sample studies have suggested the potential efficacy of SCS for nOH caused by spinal cord injury (SCI). This study innovatively proposes the use of eSCS and tSCS to improve nOH and related clinical symptoms in patients with PDS. A prospective, single-center, randomized, controlled clinical trial is planned to compare the efficacy of invasive and non-invasive SCS in treating nOH, thereby providing new insights for the effective treatment of PDS.

Interventions

• Device Epidural spinal cord stimulation
  Epidural spinal cord stimulation (eSCS) is a very thin electrode implanted in the dorsal epidural space of the spinal cord to improve the patient's symptoms by stimulating the spinal nerves with pulsed electrical currents, which attenuate or enhance the flow of nerve impulses from the periphery to the central system, i.e., stimulating thick fibres to achieve therapeutic results. SCS system consists of three components: an electrode implanted in the epidural space of the patient's spinal cord, a
• Device Transcutaneous spinal cord stimulation
  Transcutaneous spinal cord stimulation (tSCS) is a non-invasive treatment that improves symptoms by stimulating spinal nerves with pulsed electrical currents via electrodes placed at corresponding spinal cord segments. The tSCS system consists of an electrical pulse stimulator, wires, and conductive patches.

Primary outcome measures

• Change of blood pressure from baseline to immediately post-operation or post transcutaneous stimulation [Time frame: Immediately post surgery or post transcutaneous stimulation]
• Change of blood pressure from baseline to 3 months post-operation or post transcutaneous stimulation [Time frame: 3 months post surgery or post transcutaneous stimulation]
• Change of blood pressure from baseline to 6 months post-operation or post transcutaneous stimulation [Time frame: 6 months post surgery or post transcutaneous stimulation]
• Change of blood pressure from baseline to 9 months post-operation or post transcutaneous stimulation [Time frame: 9 months post surgery or post transcutaneous stimulation]
• Change of blood pressure from baseline to 12 months post-operation or post transcutaneous stimulation [Time frame: 12 months post surgery or post transcutaneous stimulation]
• Change of blood pressure from baseline to 18 months post-operation or post transcutaneous stimulation [Time frame: 18 months post surgery or post transcutaneous stimulation]
• Change of blood pressure from baseline to 24 months post-operation or post transcutaneous stimulation [Time frame: 24 months post surgery or post transcutaneous stimulation]

Secondary outcome measures (12)

• Change of oxygen desaturation index from baseline to immediately post-operation or post transcutaneous stimulation [Time frame: Immediately post surgery or post transcutaneous stimulation]
• Change of oxygen desaturation index from baseline to 3 months post-operation or post transcutaneous stimulation [Time frame: 3 months post surgery or post transcutaneous stimulation]
• Change of oxygen desaturation index from baseline to 6 months post-operation or post transcutaneous stimulation [Time frame: 6 months post surgery or post transcutaneous stimulation]
• Change of oxygen desaturation index from baseline to 9 months post-operation or post transcutaneous stimulation [Time frame: 9 months post surgery or post transcutaneous stimulation]
• Change of oxygen desaturation index from baseline to 12 months post-operation or post transcutaneous stimulation [Time frame: 12 months post surgery or post transcutaneous stimulation]
• Change of oxygen desaturation index from baseline to 18 months post-operation or post transcutaneous stimulation [Time frame: 18 months post surgery or post transcutaneous stimulation]
• Change of oxygen desaturation index from baseline to 24 months post-operation or post transcutaneous stimulation [Time frame: 24 months post surgery or post transcutaneous stimulation]
• Change of apnea hypopnea index from baseline to immediately post-operation or post transcutaneous stimulation [Time frame: Immediately post surgery or post transcutaneous stimulation]
• Change of apnea hypopnea index from baseline to 3 months post-operation or post transcutaneous stimulation [Time frame: 3 months post surgery or post transcutaneous stimulation]
• Change of apnea hypopnea index from baseline to 6 months post-operation or post transcutaneous stimulation [Time frame: 6 months post surgery or post transcutaneous stimulation]
• Change of apnea hypopnea index from baseline to 9 months post-operation or post transcutaneous stimulation [Time frame: 9 months post surgery or post transcutaneous stimulation]
• Change of apnea hypopnea index from baseline to 12 months post-operation or post transcutaneous stimulation [Time frame: 12 months post surgery or post transcutaneous stimulation]

Eligibility criteria

Inclusion criteria

• 1\. Aged between 40 and 80 years;
• 2\. No dementia as measured by the cMMSE scale (formal cMMSE score should be >20 for subjects with 1 to 6 years of formal education; cMMSE score should be >24 for subjects with >6 years of formal education);
• 3\. Able and willing to follow instruction of the researcher;
• 4\. No other conditions that the researchers consider inappropriate for inclusion:

Exclusion criteria

• 1\. Severe depression (HAMD-17 above 17 as moderate to severe) or anxiety;
• 2\. Pregnancy;
• 3\. History of alcoholism;
• 4\. No skin abnormalities;
• 5\. Non-neurological disease-related symptoms that prevent patients from participation in the study.

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

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong Un — Shanghai

Identifiers

NCT: NCT07322458 · PDS_OH_tSCS

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗