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Healthy ParticipantsEarly Phase 1BCI_LDOPANCT06729658

Dopamine and Brain Computer Interface

A Early Phase 1 study testing Madopar in people with Healthy Participants, run by Max Planck Institute for Human Cognitive and Brain Sciences at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The use of Brain-Computer Interface system (BCI system) allows for the detection of neurophysiological signals on the surface of the head and provides feedback to subjects or patients. Read more about this study

Who is it for?
Ages 18 to 80 yearsHealthy volunteers can take part
Conditions the study is for
Healthy Participants
What is being tested?
Madopar
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
22 participants
Where
1 siteGermany
Study dates
1 Oct 2017to 6 Aug 2024
Phase
Early Phase 1
Are there results?
None posted in the registry

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
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Age: between 18 and 80 years old at the time of signing the consent form
  • BCI naïve
  • MRI compatible
  • Participation in a detailed discussion on the explanation of the experiment
  • Signing of consent to participate in each experiment

Who cannot join

  • Sensory deficits (visual and auditory)
  • Wernicke's or global aphasia
  • Strong spasticity
  • Neurological and/or psychiatric diseases
  • Severe pre-existing lung or heart diseases; Gastrointestinal diseases; Malignant disease
  • Thyroid diseases
Show all 20Show fewer
  • Taking other medications
  • Narrow angle glaucoma
  • Non-age-related otological diseases
  • Stimulators (cardiac, neuro, etc.)
  • Participation in a similar study
  • Fractures or lesions in the upper extremities
  • Preceding neurosurgical procedures
  • Inability to perform the experimental tasks
  • Inability to give consent
  • Have contraindication for magnetic resonance tomography (MRI) (e.g. braces, cardiac pacemakers, metallic implants that might interfere with the MR signal, claustrophobia)
  • Severe attention and drive disorders
  • Alcohol or drug abuse
  • Pregnancy
  • Women in breastfeeding period

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences

    Leipzig, 04103

Other trials in Germany

About this study

Official title: The Effect of Dopaminergic Modulation on Brain Computer Interface Efficacy

The use of Brain-Computer Interface system (BCI system) allows for the detection of neurophysiological signals on the surface of the head and provides feedback to subjects or patients. For patients with neurological disorders who have severe motor deficits, self-generated brain signals can be translated, for example, into orthosis-supported movement of the paralyzed limb. Another possibility is to translate the brain signal into peripheral electrostimulation (functional electrical stimulation, FES), which generates muscle contraction and thus movement.

Fundamentally, BCI technology can be used as a replacement therapy when no recovery of motor function is expected. Another important application lies in improving motor training, relearning, and initiating movements. In the latter case, it is hoped that BCI training will stimulate neuroplastic mechanisms that lead to functional improvement.

Read more

Problems on the translational path to clinical application are:

  • The high interindividual variability between different people regarding learning to control the BCI system;
  • The extent of learning and motor improvement is often limited For this reason, the present study aims to investigate whether dopaminergic influence on the brain affects the effectiveness of using a BCI system in healthy subjects.
Read the detailed description

Aims of the present research project are to assess the effect of dopaminergic modulation on BCI performance in healthy elderly subjects to understand the underlying neurophysiological mechanisms. The perspective lies in the application of this approach for improved motor recovery after stroke.

Stroke is one of the most common causes of motor function impairment, and its prevalence is expected to rise due to an aging population. Stroke survivors often experience some level of spontaneous recovery of motor function during the acute stage and reach a functional plateau after which the recovery is generally slow or stagnant. Interestingly, there is emerging evidence indicating that brain-computer interface (BCI) based therapies can induce recovery beyond this plateau.

Pharmacological MRI (phMRI) is a new and promising method to study the effects of substances on brain function that can ultimately be used to unravel underlying neurobiological mechanisms behind drug action. Like most of the imaging methods it represents a progress in the investigation of brain disorders and the related function of neurotransmitter pathways in a non-invasive way with respect of the overall neuronal connectivity.

Moreover, it provides an ideal tool for translation to clinical investigations. MRI, while still behind in molecular imaging strategies compared to PET and SPECT, has the advantage to have a high spatial resolution and no need for the injection of a contrast-agent or radio-labeled molecules, thereby avoiding the repetitive exposure to ionising radiations. Functional MRI (fMRI) is extensively used in research and clinical setting, where it is generally combined with a psycho-motor task. phMRI is an adaptation of fMRI enabling the investigation of a specific neurotransmitter system, such as dopamine, under physiological or pathological conditions following activation via administration of a specific challenging drug.

The importance of the neurotransmitter dopamine (DA) for motor processes has long been known. In patients suffering from the Parkinson's disease the dopamine deficiency in the basal ganglia is known to cause strong movement-related deficits.

Recent studies suggest that DA stimulates neuronal structures, which in turn affect extensive brain regions, and thus contributes to various processes of behavioural control: both motor processes of movement control and cognitive processes in the context of perceptual categorisation, reward, motivation, and executive control. For this reason, DA is also referred to as a "teaching signal".

There's emerging evidence, that DA can be effective also for forming new stroke rehabilitation strategies. For a rehabilitation strategy to be effective, it should result in formation of new motor memories, which is anatomically mediated by networks that connect the dorsolateral prefrontal cortex, primary motor cortex, striatum, and the cerebellum. New motor memories are formed and pruned by the processes of synaptic plasticity such as LTP and LTD, which require dopaminergic signaling between the substantia nigra pars compacta and striatal medium spiny neurons in the putamen. Within the motor loops of the basal ganglia, dopaminergic binding to D1Rs facilitate desired movements, whereas binding to D2Rs inhibit undesired movements.

In addition to its role in motor drive within the basal ganglia, the dopaminergic system also potentiates visuomotor integration, which is the coordination of perceptual and action-related information. At the receptor level, D1Rs are critical for proper visuomotor integration. This system is important for relating visualized environmental information with body position, thus enabling optimal movement planning and correction. Therefore, potentiating the coordination of motor drive and visuomotor integration through dopaminergic therapy may enhance recovery after stroke.

Drugs that increase the availability of central nervous system neurotransmitters (dopamine, noradrenaline, serotonin, and acetylcholine) have been shown to exert a facilitatory effect on neuroplasticity. With this in mind, investigators have studied the effects of amphetamines, selective serotonin reuptake inhibitors, donepezil, psychostimulants such as methylphenidate, and dopaminergic agents on motor recovery after stroke. Of the aforementioned drugs, only levodopa has been shown to enhance the induction of LTP-like plasticity, practice-dependent plasticity, and motor recovery after stroke in human subjects. In addition, levodopa has a safe side effect profile and is not a controlled substance.

The most common side effect of levodopa is dyskinesia, followed by nausea, then hallucinations and dizziness. Also, there is some risk of levodopa induced dyskinesia in patients with Parkinson's disease. However, these severe side-effects generally enroll after long-term (i.e., years) intake of the drug. In addition, the risk in patients with other conditions, such as stroke, is estimated to be much lower. In fact, levodopa has been used in numerous studies that focus on motor recovery in stroke survivors without any reports of dyskinesia nor other minor or major side effects. "The literature" concludes that treating stroke survivors with levodopa is unlikely to cause levodopa-induced dyskinesia, unless there is comorbid basal ganglia damage or Parkinson's disease.

The basis of BCIs functioning is the translation of neural activity directly recorded from the subject into real-time feedback in order to train consistent brain activation patterns associated with specific mental states. Neural activity can be detected through invasive (ECoG/iEEG), or non-invasive (EEG, MEG, real-time fMRI, or NIRS) methods. The majority of studies deploy EEG based non-invasive BCIs, as they are relatively easy and fast to operate, and have good temporal and spatial characteristics, thus can be used safely and effectively to elicit functional gains in stroke survivors with persistent motor deficits and may enhance the efficacy of concurrent or associated therapies, even after individuals reach a functional plateau using traditional therapies.

Currently, the majority of BCIs that target restoration of motor function are based on motor imagery (MI). Such systems are not reliant on actual movements, but rather use the mental process of imagination of a movement. The main reason is that MI leads to the activation of the same brain areas as actual movement. Problems that arise with the motor imagery without any feedback are the lack of control of the activity as well as the lack of motivation. Using a BCI, motor imagery can be measured in real-time, thus making it possible to provide real-time feedback to the subject. Furthermore, the coupling of BCI devices with MI triggered functional electrical stimulation (FES) allows for resynchronisation of cortical activation, peripheral activation, and sensory feedback. In addition to this, some studies have argued for inclusion of virtual reality for immediate visual feedback. Combination of virtual reality based action observation and FES feedback may potentiate the motor function improvement as subjects interact with the real-time on-screen avatar. Thus, it is possible to close the circuit: the motor imagery is detected by the system, and FES is applied to the targeted muscle to help the participant carry out the movement. At the same time, an avatar performs the exact same movement (in synchrony with FES), which is displayed on the participant screen in real-time. Hence, in addition to performing the physical movement which contributes to the success of the therapy, the areas of the sensory cortex are also activated synchronously with the motor imagery via the afferent nerve impulses. This leads to the stimulation of the Hebbian plasticity, which states that neurones which are repeatedly stimulated together create common connections. This is thought to induce use-dependent plasticity and facilitate functional recovery. Such strengthening of central-peripheral connections via complimentary technologies has the potential to enhance motor function recovery through induced use-dependent plasticity and facilitate post-stroke functional recovery.

There is evidence of changes in brain activation and functional connectivity (FC) in stroke patients receiving BCI based rehabilitation therapies. They can potentially result in an increase of FC between the inferior parietal lobe and the supplementary motor area (SMA), as well as between the anterior cingulate cortex and the SMA, positively correlated with gains in Fugl-Meyer scores. Moreover, FC increases were observed between the ipsilesional thalamus and the contralesional cingulate, contralateral paracentral lobule, and the bilateral precuneus.

Being tested
Madopar, Placebo
Keywords
Dopamine, Brain Computer Interface, Motor control, Neuroplasticity, MRI, Quantitative MRI, Diffusion MRI

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MadoparDrug

    Also called Levodopa

    Experimental group participants will receive Madopar 125mg for 6 days.

  • PlaceboDrug

    Also called A pill without any active components.

    Control group participants will receive placebo for 6 days.

Study groups in NCT06729658
Study groupRoleWhat they receive
Interventional group - LevodopaExperimentalArm Description: Participants will receive Levodopa followed by BCI-mediated training for 6 days.
Receives: Drug: Madopar
Control group - PlaceboPlacebo comparatorArm Description: Participants will receive Placebo followed by BCI-mediated training for 6 days.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Changes in brain structure as assessed by MTsat

    Characterization of underlying structural changes by comprehensive assessment of brain tissue properties, allowing for sensitive detection of subtle neuroplastic changes across magnetization transfer saturation (MTsat) before and after the intervention.

    Measured: Total of 4 MRIs: 1 MRI 1 week before the intervention, 1 MRI the day before the intervention week, 1 MRI 1 day after the intervention week, and 1 MRI 1 week after.

  2. Changes in brain structure as assessed by PD

    Characterization of underlying structural changes by comprehensive assessment of brain tissue properties, allowing for sensitive detection of subtle neuroplastic changes across proton density (PD) before and after the intervention.

    Measured: Total of 4 MRIs: 1 MRI 1 week before the intervention, 1 MRI the day before the intervention week, 1 MRI 1 day after the intervention week, and 1 MRI 1 week after.

  3. Changes in brain structure as assessed by R1

    Characterization of underlying structural changes by comprehensive assessment of brain tissue properties, allowing for sensitive detection of subtle neuroplastic changes across longitudinal transverse relaxation rate R1 before and after the intervention.

    Measured: Total of 4 MRIs: 1 MRI 1 week before the intervention, 1 MRI the day before the intervention week, 1 MRI 1 day after the intervention week, and 1 MRI 1 week after.

  4. Changes in brain structure as assessed by R2*

    Characterization of underlying structural changes by comprehensive assessment of brain tissue properties, allowing for sensitive detection of subtle neuroplastic changes across effective transverse relaxation rate R2* before and after the intervention.

    Measured: Total of 4 MRIs: 1 MRI 1 week before the intervention, 1 MRI the day before the intervention week, 1 MRI 1 day after the intervention week, and 1 MRI 1 week after.

  5. White matter changes as assessed by DWI (FA)

    Characterization of underlying structural changes across fractional anisotropy (FA) before and after the intervention.

    Measured: Total of 4 MRIs: 1 MRI 1 week before the intervention, 1 MRI the day before the intervention week, 1 MRI 1 day after the intervention week, and 1 MRI 1 week after.

  6. White matter changes as assessed by DWI (MD)

    Characterization of underlying structural changes across mean diffusivity (MD) before and after the intervention.

    Measured: Total of 4 MRIs: 1 MRI 1 week before the intervention, 1 MRI the day before the intervention week, 1 MRI 1 day after the intervention week, and 1 MRI 1 week after.

  7. White matter changes as assessed by DWI (AD)

    Characterization of underlying structural changes across axial diffusivity (AD) before and after the intervention.

    Measured: Total of 4 MRIs: 1 MRI 1 week before the intervention, 1 MRI the day before the intervention week, 1 MRI 1 day after the intervention week, and 1 MRI 1 week after.

  8. White matter changes as assessed by DWI (RD)

    Characterization of underlying structural changes across radial diffusivity (RD) before and after the intervention.

    Measured: Total of 4 MRIs: 1 MRI 1 week before the intervention, 1 MRI the day before the intervention week, 1 MRI 1 day after the intervention week, and 1 MRI 1 week after.

  9. White matter changes as assessed by DWI (g-ratio)

    Characterization of underlying structural changes assessed by ratio of the inner axonal diameter to the total outer diameter (g-ratio) before and after the intervention.

    Measured: Total of 4 MRIs: 1 MRI 1 week before the intervention, 1 MRI the day before the intervention week, 1 MRI 1 day after the intervention week, and 1 MRI 1 week after.

  10. Functional connectivity changes due to neuroplasticity (rs-fMRI)

    Characterization of underlying functional changes by comprehensive assessment of brain connectivity properties using resting-state fMRI before and after the intervention.

    Measured: Total of 4 MRIs: 1 MRI 1 week before the intervention, 1 MRI the day before the intervention week, 1 MRI 1 day after the intervention week, and 1 MRI 1 week after.

  11. Functional and structural brain changes due to neuroplasticity (t-fMRI)

    Characterization of underlying functional changes by comprehensive assessment of brain activity and connectivity properties using task-based fMRI before and after the intervention.

    Measured: Total of 4 MRIs: 1 MRI 1 week before the intervention, 1 MRI the day before the intervention week, 1 MRI 1 day after the intervention week, and 1 MRI 1 week after.

Secondary outcomes (2)

  1. BCI classification accuracy

    Change in BCI classification accuracy. The BCI accuracy is calculated after each session and it is defined as the number of correctly classified trials divided by the number of total trials.

    Measured: 1 week

  2. Time needed to achieve above chance-level BCI accuracy.

    Time in days needed to achieve above chance-level BCI accuracy.

    Measured: 1 week

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Dec 2024
  2. Study start1 Oct 2017
  3. Primary completion27 Feb 2023
  4. Study completion6 Aug 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Double-blinded randomized placebo-controlled intervention with 2 arms: BCI intervention with Placebo; BCI intervention with Levodopa
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06729658
Sponsor's protocol ID
BCI_LDOPA_01
Acronym
BCI_LDOPA
Status last verified
May 2025
First submitted
27 Aug 2024
Last updated
31 May 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJL, editors. Global Burden of Disease and Risk Factors. Washington (DC): The International Bank for Reconstruction and Development / The World Bank; 2006. Available from http://www.ncbi.nlm.nih.gov/books/NBK11812/

    PubMed 21250374

  • Silvoni S, Ramos-Murguialday A, Cavinato M, Volpato C, Cisotto G, Turolla A, Piccione F, Birbaumer N. Brain-computer interface in stroke: a review of progress. Clin EEG Neurosci. 2011 Oct;42(4):245-52. doi: 10.1177/155005941104200410.

    PubMed 22208122

  • Soekadar SR, Birbaumer N, Slutzky MW, Cohen LG. Brain-machine interfaces in neurorehabilitation of stroke. Neurobiol Dis. 2015 Nov;83:172-9. doi: 10.1016/j.nbd.2014.11.025. Epub 2014 Dec 7.

    PubMed 25489973

  • Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F. Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J Neurol Sci. 1973 Dec;20(4):415-55. doi: 10.1016/0022-510x(73)90175-5. No abstract available.

    PubMed 4272516

  • Arias-Carrion O, Poppel E. Dopamine, learning, and reward-seeking behavior. Acta Neurobiol Exp (Wars). 2007;67(4):481-8. doi: 10.55782/ane-2007-1664.

    PubMed 18320725

  • Bromberg-Martin ES, Matsumoto M, Hikosaka O. Dopamine in motivational control: rewarding, aversive, and alerting. Neuron. 2010 Dec 9;68(5):815-34. doi: 10.1016/j.neuron.2010.11.022.

    PubMed 21144997

  • Cools R. Dopaminergic modulation of cognitive function-implications for L-DOPA treatment in Parkinson's disease. Neurosci Biobehav Rev. 2006;30(1):1-23. doi: 10.1016/j.neubiorev.2005.03.024. Epub 2005 Jun 1.

    PubMed 15935475

  • Saint-Cyr JA. Frontal-striatal circuit functions: context, sequence, and consequence. J Int Neuropsychol Soc. 2003 Jan;9(1):103-27. doi: 10.1017/s1355617703910125.

    PubMed 12570364

  • Seger CA. How do the basal ganglia contribute to categorization? Their roles in generalization, response selection, and learning via feedback. Neurosci Biobehav Rev. 2008;32(2):265-78. doi: 10.1016/j.neubiorev.2007.07.010. Epub 2007 Aug 12.

    PubMed 17919725

  • Beninger RJ. The role of dopamine in locomotor activity and learning. Brain Res. 1983 Oct;287(2):173-96. doi: 10.1016/0165-0173(83)90038-3.

    PubMed 6357357

  • Wise RA, Rompre PP. Brain dopamine and reward. Annu Rev Psychol. 1989;40:191-225. doi: 10.1146/annurev.ps.40.020189.001203.

    PubMed 2648975

  • Schultz W, Dayan P, Montague PR. A neural substrate of prediction and reward. Science. 1997 Mar 14;275(5306):1593-9. doi: 10.1126/science.275.5306.1593.

    PubMed 9054347

  • Gerfen CR, Surmeier DJ. Modulation of striatal projection systems by dopamine. Annu Rev Neurosci. 2011;34:441-66. doi: 10.1146/annurev-neuro-061010-113641.

    PubMed 21469956

  • Colzato LS, van Wouwe NC, Hommel B. Feature binding and affect: emotional modulation of visuo-motor integration. Neuropsychologia. 2007 Jan 28;45(2):440-6. doi: 10.1016/j.neuropsychologia.2006.06.032. Epub 2006 Aug 22.

    PubMed 16926036

  • Jenner P. Molecular mechanisms of L-DOPA-induced dyskinesia. Nat Rev Neurosci. 2008 Sep;9(9):665-77. doi: 10.1038/nrn2471.

    PubMed 18714325

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Madopar in people with Healthy Participants, run by Max Planck Institute for Human Cognitive and Brain Sciences at 1 site in Germany.

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 20 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: finished, as of the sponsor's last update on 31 May 2025. 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 Germany. 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.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes in brain structure as assessed by MTsat (time frame: Total of 4 MRIs: 1 MRI 1 week before the intervention, 1 MRI the day before the intervention week, 1 MRI 1 day after the intervention week, and 1 MRI 1 week after.). The study lists 11 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 NCT06729658, which also lists 26 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 31 May 2025.

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Dopamine and Brain Computer Interface (NCT06729658) | AzTrials