rTMS as an Intervention for Levodopa-induced Dyskinesia

NCT06570824 | Recruiting DMC

• 1 other identifier: ADAPT-LIDI
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed study investigates the use of repetitive transcranial magnetic stimulation (rTMS) as a treatment for levodopa-induced dyskinesia (LID) in Parkinson's Disease (PD). Specifically, the study aims to determine whether patterned stimulation of the pre-supplementary motor area (pre-SMA) can delay the onset of LID after levodopa intake and reduce LID severity in PD patients. This study will provide critical insights into potential targets for rTMS treatment, optimal rTMS parameters, and the mechanisms underlying LID in Parkinson's disease.

Conditions

Dyskinesia, Drug-Induced; Parkinson Disease

Keywords

Basal Ganglia Diseases; Parkinson's Disease; Central Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Dyskinesias; LID; Levodopa induced dyskinesia; Pre-SMA

Outcome Measures

Primary Outcomes (2)

• Unified Dyskinesia Rating Scale (UDysRS)

  UDysRS utilizes rater information, patient self-report and objective measures of dyskinesia to provide assessments of impairment and disability due to dyskinesia.The UDysRS total score ranges from 0 to 104 with a lower score indicating less dyskinesia.

  Baseline (usual medication intake) and up to 40 minutes after taking 150 % of normal morning levodopa dose as Madopar Quick

• Dyskinesia onset time

  The onset time of dyskinesia in minutes after levodopa administration

  Baseline (usual medication intake) and up to 40 minutes after taking 150 % of normal morning levodopa dose as Madopar Quick

Secondary Outcomes (1)

• Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS)

  Baseline (usual medication intake) and up to 40 minutes after taking 150 % of normal morning levodopa dose as Madopar Quick

Other Outcomes (9)

• TMS adverse events and associated sensations questionnaire (TMSens_Q)

  Immediately after the TMS intervention (sham and active)

• Transcranial evoked potentials (TEPs)

  Before and immediately after the TMS intervention (sham and active), up to 20 minutes after taking 150 % of normal morning levodopa dose as Madopar Quick

• Event related potentials (ERPs)

  Immediately after taking 150 % of normal morning levodopa dose as Madopar Quick

Study Arms (4)

Gamma burst rTMS

ACTIVE COMPARATOR

Real stimulation with 4 pulses at the frequency of 130Hz repeating at 1 Hz will be delivered on the pre-SMA using the active side of the coil for 30 minutes

Device: active TMS

Sham gamma burts rTMS

SHAM COMPARATOR

Sham stimulation with 4 pulses at the frequency of 130Hz repeating at 1Hz will be delivered on the pre-SMA with a non-active side of the coil for 30 minutes

Device: sham TMS

Beta burst rTMS

ACTIVE COMPARATOR

Real stimulation with 4 pulses at the frequency of 20Hz repeating at 1 Hz be delivered on the pre-SMA using the active side of the coil for 30 minutes

Device: active TMS

Sham beta burst rTMS

SHAM COMPARATOR

Sham stimulation with 4 pulses at the frequency of 20Hz repeating at 1Hz will be delivered on the pre-SMA with a non-active side of the coil for 30 minutes

Device: sham TMS

Interventions

active TMS DEVICE

Transcranial magnetic stimulation using MagVenture XP Orange Stimulator using active side of MagVenture Cool-B70 coil

Beta burst rTMS; Gamma burst rTMS

sham TMS DEVICE

Sham transcranial magnetic stimulation using MagVenture XP Orange Stimulator, flipping the active side of the MagVenture Cool-B70 coil

Sham beta burst rTMS; Sham gamma burts rTMS

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinically established or probable PD
• Clinical Diagnostic Criteria for Parkinson's Disease
• Peak-of-dose levodopa-induced dyskinesia.
• Stable antiparkinsonian medicine for at least four weeks.
• Signed informed consent.

You may not qualify if:

• Psychiatric disorders.
• Usage of antipsychotic medication, Donepezil, and GABAergic medications (such as pregabalin and gabapentin).
• Regular usage of benzodiazepines and opioids (more than once per week).
• History of neurological disease other than Parkinson's disease.
• History of epilepsy/conditions associated with increased risk to seizure-induction through TMS.
• Close relatives suffering from epilepsy/conditions associated with increased risk to seizure-induction through TMS.
• Contraindications for MRI scan
• Female participants of childbearing age must not be pregnant and that they must use contraception during the trial.
• Refuse to be informed about new health related information and accidental health related findings that might appear through participation in the study.

Sponsors & Collaborators

• Danish Research Centre for Magnetic Resonance: lead

Study Sites (1)

DRCMR

Hvidovre, 2650, Denmark

RECRUITING

Related Publications (2)

• Lohse A, Meder D, Nielsen S, Lund AE, Herz DM, Lokkegaard A, Siebner HR. Low-frequency transcranial stimulation of pre-supplementary motor area alleviates levodopa-induced dyskinesia in Parkinson's disease: a randomized cross-over trial. Brain Commun. 2020 Sep 18;2(2):fcaa147. doi: 10.1093/braincomms/fcaa147. eCollection 2020.

  PMID: 33225277 BACKGROUND

• Herz DM, Haagensen BN, Christensen MS, Madsen KH, Rowe JB, Lokkegaard A, Siebner HR. The acute brain response to levodopa heralds dyskinesias in Parkinson disease. Ann Neurol. 2014 Jun;75(6):829-36. doi: 10.1002/ana.24138. Epub 2014 May 28.

  PMID: 24889498 BACKGROUND

Related Links

• Institutional website

MeSH Terms

Conditions

Dyskinesia, Drug-Induced; Parkinson Disease; Basal Ganglia Diseases; Central Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Dyskinesias

Condition Hierarchy (Ancestors)

Nervous System Diseases; Neurologic Manifestations; Neurotoxicity Syndromes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Poisoning; Parkinsonian Disorders; Brain Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Hartwig R. Siebner, Prof.

  Head of Research, Prof, DMSc

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laura Sakalauskaite, MD

CONTACT

+45 38621184; laura.sakalauskaite.01@regionh.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants will receive sham rTMS by flipping the coil upside down. This will still provide similar sensory experience as an active stimulation that the patients will not distinguish between. Dyskinesia assessment is filmed during the visit and an experienced rater is unaware of a treatment condition of the patient.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Research, Prof, DMSc

Model Details: The study has a double-blinded crossover design. The research participants will, in two separate stimulation sessions, receive either real rTMS treatment or a sham-TMS stimulation. The session order (real rTMS first or sham first) will be randomised between research participants. The research participant will be blinded to which treatment (real or sham) they receive at any session. There will be two sequential groups of patients. First group will receive gamma burst rTMS stimulation and sham and the other group will receive beta burst rTMS and sham.

Study Record Dates

• First Submitted: May 3, 2024
• First Posted: August 26, 2024
• Study Start: July 22, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: August 28, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Time Frame: After study completion
• Access Criteria: Anonymised data, reasonable request

Locations

DK (1)