rTMS and Olfactory Training for Parkinson's Disease

NCT07666477 | Completed

• 1 other identifier: 2025/02-04
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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.

Conditions

Parkinson Disease (PD); Olfactory Dysfunction

Keywords

repetitive Transcranial Magnetic Stimulation; Parkinson's Disease; Olfactory Training; Chemosensory Dysfunction; Non-invasive Neuromodulation

Outcome Measures

Primary Outcomes (1)

• Change in Sniffin' Sticks TDI Score from Baseline to Week 12

  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).

  Baseline and 12 weeks.

Secondary Outcomes (3)

• Change in Sniffin' Sticks Odor Threshold Score from Baseline to Week 12

  Baseline and 12 weeks.

• Change in Sniffin' Sticks Odor Discrimination Score from Baseline to Week 12

  Baseline and 12 weeks.

• Change in Sniffin' Sticks Odor Identification Score from Baseline to Week 12

  Baseline and 12 weeks.

Study Arms (4)

rTMS and Olfactory Training

EXPERIMENTAL

Participants in this group receive high-frequency (10 Hz) rTMS stimulation (2000 pulses per session) targeted at cortical olfactory regions, combined with a daily structured olfactory training protocol over the 12-week study period.

Device: Repetitive Transcranial Magnetic Stimulation (rTMS); Behavioral: Structured Olfactory Training

Experimental: rTMS alone

EXPERIMENTAL

Participants in this group receive high-frequency (10 Hz) rTMS stimulation (2000 pulses per session) targeted at cortical olfactory regions, without the concurrent structured olfactory training protocol, over the 12-week study period.

Device: Repetitive Transcranial Magnetic Stimulation (rTMS)

Active Comparator: Olfactory Training alone

ACTIVE COMPARATOR

Participants in this group perform a structured 12-week olfactory training protocol twice daily using standardized odorants, without receiving any active rTMS stimulation.

Behavioral: Structured Olfactory Training

Sham Comparator: Control Group

SHAM COMPARATOR

Participants in this group receive sham rTMS stimulation (using a deactivated coil setup) without any structured olfactory training for the 12-week study duration.

Device: Sham rTMS

Interventions

Repetitive Transcranial Magnetic Stimulation (rTMS) DEVICE

High-frequency (10 Hz) rTMS stimulation (2000 pulses per session) targeted at cortical olfactory regions.

Experimental: rTMS alone; rTMS and Olfactory Training

Structured Olfactory Training BEHAVIORAL

Daily structured olfactory training protocol using standardized odorants (twice daily).

Active Comparator: Olfactory Training alone; rTMS and Olfactory Training

Sham rTMS DEVICE

Sham stimulation delivered using an identical coil setup without neural activation.

Sham Comparator: Control Group

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mustafa Baran: lead
• Batman University: collaborator

Study Sites (1)

Batman University

Batman, Batman, 72060, Turkey (Türkiye)

Location

Related Publications (4)

• Kobal G, Klimek L, Wolfensberger M, Gudziol H, Temmel A, Owen CM, Seeber H, Pauli E, Hummel T. Multicenter investigation of 1,036 subjects using a standardized method for the assessment of olfactory function combining tests of odor identification, odor discrimination, and olfactory thresholds. Eur Arch Otorhinolaryngol. 2000;257(4):205-11. doi: 10.1007/s004050050223.

  PMID: 10867835 BACKGROUND

• Lefaucheur JP, Aleman A, Baeken C, Benninger DH, Brunelin J, Di Lazzaro V, Filipovic SR, Grefkes C, Hasan A, Hummel FC, Jaaskelainen SK, Langguth B, Leocani L, Londero A, Nardone R, Nguyen JP, Nyffeler T, Oliveira-Maia AJ, Oliviero A, Padberg F, Palm U, Paulus W, Poulet E, Quartarone A, Rachid F, Rektorova I, Rossi S, Sahlsten H, Schecklmann M, Szekely D, Ziemann U. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014-2018). Clin Neurophysiol. 2020 Feb;131(2):474-528. doi: 10.1016/j.clinph.2019.11.002. Epub 2020 Jan 1.

  PMID: 31901449 BACKGROUND

• Hummel T, Rissom K, Reden J, Hahner A, Weidenbecher M, Huttenbrink KB. Effects of olfactory training in patients with olfactory loss. Laryngoscope. 2009 Mar;119(3):496-9. doi: 10.1002/lary.20101.

  PMID: 19235739 BACKGROUND

• Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, Obeso J, Marek K, Litvan I, Lang AE, Halliday G, Goetz CG, Gasser T, Dubois B, Chan P, Bloem BR, Adler CH, Deuschl G. MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord. 2015 Oct;30(12):1591-601. doi: 10.1002/mds.26424.

  PMID: 26474316 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Mustafa BARAN, PhD

  Batman University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Model Details: 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.

Study Record Dates

• First Submitted: June 18, 2026
• First Posted: June 24, 2026
• Study Start: January 2, 2026
• Primary Completion: May 15, 2026
• Study Completion: May 21, 2026
• Last Updated: June 26, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: The datasets will be available upon publication of the study results and will remain accessible for a period of 5 years following the publication date.
• Access Criteria: Qualified researchers who wish to access the IPD and supporting information (study protocol, statistical analysis plan, clinical study report) may submit a formal request to the corresponding author via email. The request must include a description of the intended research and evidence of institutional ethics committee approval. Data will be shared for valid scientific purposes, subject to a signed data sharing agreement to ensure participant confidentiality.

Locations

TU (1)