Olfactory Dysfunction, Parkinson Disease (PD)
Conditions
Keywords
repetitive Transcranial Magnetic Stimulation, Parkinson's Disease, Olfactory Training, Chemosensory Dysfunction, Non-invasive Neuromodulation
Brief summary
Background: Olfactory and gustatory impairments are common clinical manifestations in patients with neurodegenerative conditions like Parkinson's disease. These chemosensory deficits significantly impact the quality of life, often preceding motor symptoms. Currently, there is a need for effective non-invasive interventions to improve sensory recovery. Objective: The primary objective of this study is to evaluate the therapeutic efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) combined with olfactory training in restoring chemosensory function. We aim to determine whether this combined approach provides superior outcomes compared to individual therapies or standard care. Methods: This clinical trial involves 120 patients diagnosed with Parkinson's disease. Participants will be randomized into four groups to receive either combined rTMS and olfactory training, isolated rTMS, isolated olfactory training, or a control intervention. The recovery of olfactory function will be measured using validated sensory testing tools (such as Sniffin' Sticks) and Electrogustometry (EGM) to assess neural pathway improvement. Conclusion/Significance: This study aims to provide evidence-based insights into non-invasive neurological rehabilitation for chemosensory dysfunction. The findings may help optimize personalized treatment protocols for patients suffering from sensory impairment, potentially enhancing their overall cognitive and sensory quality of life.
Detailed description
Study Design and Patient Selection: This is a prospective, randomized, four-arm clinical study. A total of 120 patients meeting the inclusion criteria for Parkinson's disease-related chemosensory dysfunction are enrolled. Subjects are randomized using a 1:1:1:1 ratio. Intervention Protocols: rTMS Protocol: The intervention group receives high-frequency (10 Hz) stimulation targeted at the cortical regions associated with olfactory processing. The protocol consists of 2000 pulses per session. Olfactory Training: Participants perform structured olfactory training utilizing standardized odorant sets, conducted twice daily over the 12-week study period. Methodological Blinding: To ensure task compliance and methodological rigor, distilled water is utilized as a sensory blind check during testing procedures. Measurements: Sensory assessments are focused on the lateral margins of the tongue using Electrogustometry (EGM) and standardized smell sensitivity tests. Changes in function are recorded using the Visual Analog Scale (VAS) at baseline and 12-week follow-up intervals. Statistical Analysis: Data is analyzed to compare the mean sensory threshold changes between the four groups. Baseline characteristics and longitudinal improvements are evaluated using ANOVA followed by post-hoc analysis to determine the statistical significance of the combined therapy versus monotherapy and control groups.
Interventions
DEVICERepetitive Transcranial Magnetic Stimulation (rTMS)
High-frequency (10 Hz) rTMS stimulation (2000 pulses per session) targeted at cortical olfactory regions.
BEHAVIORALStructured Olfactory Training
Daily structured olfactory training protocol using standardized odorants (twice daily).
DEVICESham rTMS
Sham stimulation delivered using an identical coil setup without neural activation.
Sponsors
Mustafa Baran
Batman University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Participants are blinded to their assigned intervention arm, as they receive either active rTMS or sham stimulation, which are delivered using an identical setup. Outcome assessors, who perform the chemosensory evaluations (e.g., Sniffin' Sticks test), are also blinded to the group assignment of each participant to minimize assessment bias. Investigators involved in the analysis are masked to the group identities until the data collection phase is finalized.
Intervention model description
Participants are randomized into four distinct groups (1:1:1:1 ratio) to receive their respective interventions simultaneously. Each participant remains within their assigned group throughout the entire 12-week study period, with no crossover between intervention protocols, ensuring independent assessment of the therapeutic effects for each group.
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients aged between 40 and 75 years. * Confirmed diagnosis of idiopathic Parkinson's disease (PD) according to the Movement Disorder Society (MDS) clinical diagnostic criteria. * Confirmed olfactory dysfunction validated by the Sniffin' Sticks test at baseline (defined as a composite TDI score ≤ 30.5 for hyposmia and \< 16.0 for functional anosmia).
Exclusion criteria
* Presence of cranial metal implants or cardiac pacemakers (absolute contraindications for rTMS). * Pregnancy. * Severe psychiatric disorders. * Advanced dementia. * History of nasal polyps or active sinusitis that could mechanically obstruct olfactory pathways.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Sniffin' Sticks TDI Score from Baseline to Week 12 | Baseline and 12 weeks. | The Sniffin' Sticks test evaluates olfactory function through Threshold, Discrimination, and Identification (TDI) scores. The primary endpoint is the mean change in the composite TDI score (range 1-48) from the start of the study (Baseline) to the end of the intervention (Week 12). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Sniffin' Sticks Odor Threshold Score from Baseline to Week 12 | Baseline and 12 weeks. | The Sniffin' Sticks Odor Threshold Subtest evaluates olfactory sensory thresholds. Scores on this subtest range from a minimum of 1 to a maximum of 16. Higher scores indicate better olfactory function (a more sensitive odor threshold). The endpoint is the mean change in the odor threshold score from the start of the study (Baseline) to the end of the intervention (Week 12). |
| Change in Sniffin' Sticks Odor Discrimination Score from Baseline to Week 12 | Baseline and 12 weeks. | The Sniffin' Sticks Odor Discrimination Subtest evaluates the ability to differentiate between distinct odorants. Scores on this subtest range from a minimum of 1 to a maximum of 16. Higher scores indicate better olfactory function. The endpoint is the mean change in the odor discrimination score from the start of the study (Baseline) to the end of the intervention (Week 12). |
| Change in Sniffin' Sticks Odor Identification Score from Baseline to Week 12 | Baseline and 12 weeks. | The Sniffin' Sticks Odor Identification Subtest evaluates the cognitive ability to identify specific odorants. Scores on this subtest range from a minimum of 1 to a maximum of 16. Higher scores indicate better olfactory function. The endpoint is the mean change in the odor identification score from the start of the study (Baseline) to the end of the intervention (Week 12). |
Countries
Turkey (Türkiye)
Contacts
PRINCIPAL_INVESTIGATORMustafa BARAN, PhD
Batman University
Outcome results
None listed