Dyskinesia, Drug-InducedADAPT-LIDINCT06570824
rTMS as an Intervention for Levodopa-induced Dyskinesia
A study testing active TMS in people with Dyskinesia, Drug-Induced and Parkinson Disease, run by Danish Research Centre for Magnetic Resonance at 1 site in Denmark.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Dyskinesia, Drug-Induced, Parkinson Disease
- What is being tested?
- active TMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 68 participants
- Where
- 1 siteDenmark
- Study dates
- 22 Aug 2024to 1 Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark1 site, 1 recruiting
- Recruiting
DRCMR
Hvidovre, 2650
Hartwig Siebner, Prof
About this study
Official title: Network Based Repetitive Transcranial Magnetic Stimulation (rTMS) as an Intervention for Levodopa-induced Dyskinesia (LID) in Parkinson's Disease (PD)
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.
Read the detailed description
Long-term use of levodopa in Parkinson's Disease (PD) often leads to motor complications, such as Levodopa-Induced Dyskinesia, which significantly impacts patients' daily lives. Various brain regions have been targeted for treatment with Transcranial Magnetic Stimulation (TMS), including the supplementary motor area (SMA), primary motor cortex, cerebellum, and prefrontal cortex. Specifically, targeting the pre-SMA with 1-Hz rTMS has been shown to delay and reduce dyskinesia severity in PD patients following levodopa administration. These findings suggest that the pre-supplementary motor area is a promising target for brain stimulation therapy, as it plays a causal role in the pathophysiology of peak-of-dose dyskinesia.
The current study aims to build on previous research by optimizing the stimulation intensity and location based on individual neuroanatomy and simulated electric fields. Additionally, the study will explore the impact of rTMS delivered in short high-frequency bursts, differing from the single rTMS pulses used in previous studies. In the context of LID, Deep Brain Stimulation (DBS) typically targets the subthalamic nucleus (STN) using gamma frequencies (40-200 Hz, most commonly 130 Hz). Drawing from this principle, the study posits that delivering rTMS bursts at gamma frequencies to the pre-SMA will effectively mitigate LID symptoms. Moreover, evidence from cortical brain rhythm recordings highlights that beta frequencies (12-30 Hz), which are crucial for movement control and are disrupted in PD, may also hold therapeutic potential. Therefore, the study will investigate whether rTMS bursts at beta frequencies could similarly reduce LID symptoms. Given the absence of prior research directly comparing the effects of different burst frequencies on LID, the study will systematically apply two distinct burst frequencies, in separate patient groups, to determine which, if either, produces a meaningful reduction in LID symptoms.
Dyskinesia onset time and severity will be measured using the Unified Dyskinesia Rating Scale (UDysRS) and assessed by a clinician rater who is blinded to the treatment condition. The results will be compared between the active and sham stimulation conditions.
- Conditions
- Dyskinesia, Drug-Induced, Parkinson Disease
- Being tested
- active TMS, sham TMS
- Keywords
- Basal Ganglia Diseases, Parkinson's Disease, Central Nervous System Diseases, Movement Disorders, Synucleinopathies, Neurodegenerative Diseases, Dyskinesias, LID, Levodopa induced dyskinesia, Pre-SMA
- Medical subject headings
- Dyskinesia, Drug-Induced, Parkinson Disease, Basal Ganglia Diseases, Central Nervous System Diseases, Movement Disorders, Synucleinopathies, Neurodegenerative Diseases, Dyskinesias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
active TMSDevice
Transcranial magnetic stimulation using MagVenture XP Orange Stimulator using active side of MagVenture Cool-B70 coil
sham TMSDevice
Sham transcranial magnetic stimulation using MagVenture XP Orange Stimulator, flipping the active side of the MagVenture Cool-B70 coil
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: 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 Receives: Device: sham TMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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)
Measure the changes of scores of United Parkinson's Disease Rating Scale Part III in active stimulation compared to sham. The total scores range from 0 (good health) to 132 (poor health).
Measured: Baseline (usual medication intake) and up to 40 minutes after taking 150 % of normal morning levodopa dose as Madopar Quick
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2024
- Study start22 Aug 2024
- Primary completion1 May 2027 (estimated)
- Study completion1 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Dyskinesia, Drug-InducedStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 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.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 68 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Danish Research Centre for Magnetic Resonance
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hartwig R. Siebner, Danish Research Centre for Magnetic Resonance
- Investigators
- Hartwig R. Siebner, Prof., Principal investigator, Head of Research, Prof, DMSc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06570824
- Sponsor's protocol ID
- ADAPT-LIDI
- Acronym
- ADAPT-LIDI
- Status last verified
- Aug 2026
- First submitted
- 3 May 2024
- Last updated
- 27 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Sharing of anonymised data
Publications
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.
PubMed 33225277Herz 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.
PubMed 24889498
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Network Based Repetitive Transcranial Magnetic Stimulation (rTMS) as an Intervention for Levodopa-induced Dyskinesia (LID) in Parkinson's Disease (PD)
- ClinicalTrials.gov ID
- NCT06570824
- Acronym / sponsor ID
- ADAPT-LIDI / ADAPT-LIDI
- Conditions
- Dyskinesia, Drug-Induced, Parkinson Disease
- Keywords
- Basal Ganglia Diseases, Parkinson's Disease, Central Nervous System Diseases, Movement Disorders, Synucleinopathies, Neurodegenerative Diseases, Dyskinesias, LID
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 68 participants (estimated)
- Lead sponsor
- Danish Research Centre for Magnetic ResonanceUniversity, hospital or other
- Study start
- 22 Aug 2024 (actual)
- Primary completion
- 1 May 2027 (estimated)
- Study completion
- 1 Dec 2027 (estimated)
- First posted
- 26 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Long-term use of levodopa in Parkinson's Disease (PD) often leads to motor complications, such as Levodopa-Induced Dyskinesia, which significantly impacts patients' daily lives. Various brain regions have been targeted for treatment with Transcranial Magnetic Stimulation (TMS), including the supplementary motor area (SMA), primary motor cortex, cerebellum, and prefrontal cortex. Specifically, targeting the pre-SMA with 1-Hz rTMS has been shown to delay and reduce dyskinesia severity in PD patients following levodopa administration. These findings suggest that the pre-supplementary motor area is a promising target for brain stimulation therapy, as it plays a causal role in the pathophysiology of peak-of-dose dyskinesia.
The current study aims to build on previous research by optimizing the stimulation intensity and location based on individual neuroanatomy and simulated electric fields. Additionally, the study will explore the impact of rTMS delivered in short high-frequency bursts, differing from the single rTMS pulses used in previous studies. In the context of LID, Deep Brain Stimulation (DBS) typically targets the subthalamic nucleus (STN) using gamma frequencies (40-200 Hz, most commonly 130 Hz). Drawing from this principle, the study posits that delivering rTMS bursts at gamma frequencies to the pre-SMA will effectively mitigate LID symptoms. Moreover, evidence from cortical brain rhythm recordings highlights that beta frequencies (12-30 Hz), which are crucial for movement control and are disrupted in PD, may also hold therapeutic potential. Therefore, the study will investigate whether rTMS bursts at beta frequencies could similarly reduce LID symptoms. Given the absence of prior research directly comparing the effects of different burst frequencies on LID, the study will systematically apply two distinct burst frequencies, in separate patient groups, to determine which, if either, produces a meaningful reduction in LID symptoms.
Dyskinesia onset time and severity will be measured using the Unified Dyskinesia Rating Scale (UDysRS) and assessed by a clinician rater who is blinded to the treatment condition. The results will be compared between the active and sham stimulation conditions.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 4
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Gamma burst rTMS | Active comparator | Device: active TMSReal 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 |
| Sham gamma burts rTMS | Sham comparator | Device: sham TMSSham 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 |
| Beta burst rTMS | Active comparator | Device: active TMSReal 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 |
| Sham beta burst rTMS | Sham comparator | Device: sham TMSSham 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 |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| active TMSTranscranial magnetic stimulation using MagVenture XP Orange Stimulator using active side of MagVenture Cool-B70 coil | Device | Beta burst rTMS, Gamma burst rTMS |
| sham TMSSham transcranial magnetic stimulation using MagVenture XP Orange Stimulator, flipping the active side of the MagVenture Cool-B70 coil | Device | Sham beta burst rTMS, Sham gamma burts rTMS |
Primary outcome
Unified Dyskinesia Rating Scale (UDysRS)
Time frame: Baseline (usual medication intake) and up to 40 minutes after taking 150 % of normal morning levodopa dose as Madopar Quick
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.
Dyskinesia onset time
Time frame: Baseline (usual medication intake) and up to 40 minutes after taking 150 % of normal morning levodopa dose as Madopar Quick
The onset time of dyskinesia in minutes after levodopa administration
1 secondary outcome
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS)
Time frame: Baseline (usual medication intake) and up to 40 minutes after taking 150 % of normal morning levodopa dose as Madopar Quick
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2026.
- Background: PubMed 33225277Lohse 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.
- Background: PubMed 24889498Herz 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.
- Institutional websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Sharing of anonymised data
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Hartwig R. Siebner, Prof. principal investigator
Head of Research, Prof, DMSc
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing active TMS in people with Dyskinesia, Drug-Induced and Parkinson Disease, run by Danish Research Centre for Magnetic Resonance at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Laura Sakalauskaite, MD (+45 38621184, laura.sakalauskaite.01@regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Unified Dyskinesia Rating Scale (UDysRS) (time frame: Baseline (usual medication intake) and up to 40 minutes after taking 150 % of normal morning levodopa dose as Madopar Quick). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06570824, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2026.