Idiopathic Parkinson's DiseaseDEINCT03665493
Dopamine Effect on Inhibitory Control
A study testing PD patients H&Y=1.5-2 Medications ON, PD patients H&Y=1.5-2 Medications OFF and PD patients H&Y=3 Medications OFF in people with Idiopathic Parkinson's Disease, run by Giovanni Mirabella at 1 site in Italy.
Trial summary
The effect of Levodopa medication on inhibitory control in Parkinson's patients is extremely debated despite the fact that this has potential clinical and therapeutic implications. A key confounding factor of many previous studies is that they did not take the disease duration in consideration. Read more about this study
- Who is it for?
- Ages 40 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Idiopathic Parkinson's Disease
- What is being tested?
- PD patients H&Y=1.5-2 Medications ON, PD patients H&Y=1.5-2 Medications OFF and PD patients H&Y=3 Medications OFF
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteItaly
- Study dates
- 30 Sep 2020to 10 Nov 2023
- Phase
- Interventional
- 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 40 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Right-handedness (as assessed by the Edinburgh Handedness Inventory)
- Being in stable treatment with the administration of L-dopa and dopamine agonists (i.e. not having motor fluctuations and/or dyskinesia)
- Having a Hoehn \& Yahr score between 1.5 and 3
Who cannot join
- Presence of severe sensory deficits
- Presence of overt signs of dementia (a. mini-mental state examination, MMSE must be ≥24; b. intelligence quotient ≥75).
- Comorbidity with other psychiatric disorders that might interfere with task execution (i.e. attentional disorders).
- Presence of severe tremor or rigidity of the right arm in the OFF medication state.
Trial locations and contacts
1 site in 1 country.
About this study
The effect of Levodopa medication on inhibitory control in Parkinson's patients is extremely debated despite the fact that this has potential clinical and therapeutic implications. A key confounding factor of many previous studies is that they did not take the disease duration in consideration. In fact, in moderate-to-advanced stages of Parkinson dopaminergic drugs could not produce a clear effect because too few dopaminergic cells for the drugs to operate on survived. Hence, in this study, we will compare the performance in the stop signal task in early-stage versus moderate-to-advanced stages Parkinson's patients both in ON and in OFF medication. In addition, to have a baseline measure of inhibitory control we will compare patient's performances with that of age-matched subjects.
Read the detailed description
The ability to stop a pending action is fundamental for survival in a natural environment where events cannot be fully predicted. Sudden events, such as the appearance of a physical obstacle, often require a quick change of the planned motor strategy and the first step toward this goal is to suppress the pre-programmed actions. Thus voluntary inhibition plays a crucial role in cognitive control and behavioral flexibility (1, 2). It has been shown that Parkinson's patients suffer from a specific deficit in this functions (3, 4, 5). However, it is extremely debated whether and how Levodopa medication (levodopa, dopamine agonists, anticholinergic drugs, or a combination of levodopa and an anticholinergic drug) affects response inhibition. A number of studies measuring inhibitory control via the stop signal task in Parkinson's patients seem to indicate that dopaminergic medications do not influence this executive function (5, 6, 7). However, a recent study (8) found that Levodopa medication does not affect specifically inhibitory control or movement readiness, but the balance between them. In fact, Parkinson's patients in the OFF medication state were able to maintain response latencies in the same range as healthy controls, but they showed a significant reduction in the ability to stop reactions abruptly. In contrast, patients' performance shifted significantly when taking dopaminergic medications. They move slower but stopping improved relative to the off dopamine state. This pattern suggests a role for dopamine in modulating the tradeoff between the two action control processes. In addition, studies of other specific populations and healthy adults suggest that dopaminergic medications deserve reconsideration in response inhibition. For instance, positron emission (PET) studies have found that higher levels of striatal D1 and D2/D3 receptor availability predict better performance on the stop signal task (9, 10) and that response inhibition performance evokes dopamine release in prefrontal, parietal, and temporal cortex in healthy adults (11). Even more importantly, a few recent studies provided evidence that early-stage Parkinson's patients with response inhibition impairment seem to benefit from dopaminergic treatment (12,13). Therefore, a plausible hypothesis is that the absence of a clear effect of dopaminergic medications could be ascribed to the fact that in most previous studies included Parkinson's patients in the moderate-to-advanced stages. In those patients, the diminished efficacy of dopaminergic drugs could be a consequence that too few dopaminergic cells for the drugs to operate on survived (14).
Hence, the aim of the present work is to re-assess the impact of dopaminergic medications on inhibitory control on Parkinson's patients using a reaching version of the stop signal task (e.g. 4, 15, 16, 17, 18) taking the disease duration in consideration. To this aim, the investigators will compare the performance in the stop signal task in early-stage versus moderate-to-advanced stages Parkinson's patients both in ON and in OFF medication. Finally, to have a baseline measure of inhibitory control the investigators will compare patients' performances with those of age-matched subjects.
- Conditions
- Idiopathic Parkinson's Disease
- Being tested
- PD patients H&Y=1.5-2 Medications ON, PD patients H&Y=1.5-2 Medications OFF, Healthy age-matched controls, PD patients H&Y=3 Medications OFF, PD patients H&Y=3 Medications ON
- Keywords
- Levodopa medication, stop signal task, inhibitory control, Parkinson's Disease, stop signal reaction time, proactive inhibition
- Medical subject headings
- Parkinson Disease, Proactive Inhibition
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PD patients H&Y=1.5-2 Medications ONDrug
Parkinson's patients will be allowed to the first-morning dose of levodopa medicament (levodopa, dopamine agonists, anticholinergic drugs, or a combination of levodopa and an anticholinergic drug) which normally allowed the patient to attain the best control of symptoms one hour before being tested (19). Patients will perform both the stop-signal task and the go-only task. Experimental conditions will be counterbalanced across patients.
PD patients H&Y=1.5-2 Medications OFFDrug
Parkinson's patients will not take medications overnight prior to the study (20). Patients will perform both the stop-signal task and the go-only task. Experimental conditions will be counterbalanced across patients. This intervention will be given on a different day with respect to the Medication ON intervention. The order of intervention will be counterbalanced across subjects
Healthy age-matched controlsBehavioural
Healthy controls will perform the stop signal task and the go-only task in the same day. The order of administration will be counterbalanced.
PD patients H&Y=3 Medications OFFDrug
Parkinson's patients will not take medications overnight prior to the study (20). Patients will perform both the stop-signal task and the go-only task. Experimental conditions will be counterbalanced across patients. This intervention will be given on a different day with respect to the Medication ON intervention. The order of intervention will be counterbalanced across subjects
PD patients H&Y=3 Medications ONDrug
Parkinson's patients will be allowed to the first-morning dose of levodopa medicament (levodopa, dopamine agonists, anticholinergic drugs, or a combination of levodopa and an anticholinergic drug) which normally allowed the patient to attain the best control of symptoms one hour before being tested (19). Patients will perform both the stop-signal task and the go-only task. Experimental conditions will be counterbalanced across patients.
| Study group | Role | What they receive |
|---|---|---|
| PD patients H&Y=1.5-2 Medications ON | Experimental | Idiopathic Parkinson's patient's with Hoehn and Yahr score of 1.5- 2 i.e. in an early stage of the disease, under stable treatment with the administration of L-dopa and dopamine agonists. Patients will not present severe sensory deficits or any other neurological disease besides PD, as will be assessed by a standard neurological examination, and they will be all right-handed as will be assessed by the Edinburgh handedness inventory. Age range: 40-70 Receives: Drug: PD patients H&Y=1.5-2 Medications ON |
| PD patients H&Y=3 Medications ON | Experimental | Parkinson's patient's with Hoehn and Yahr score of 3, i.e. in moderate-to-advanced stages of the disease under stable treatment with the administration of L-dopa and dopamine agonists. Patients will not present severe sensory deficits or any other neurological disease besides PD, as will be assessed by a standard neurological examination, and they will be all right-handed as will be assessed by the Edinburgh handedness inventory. Age range: 40-70 Receives: Drug: PD patients H&Y=3 Medications ON |
| PD patients H&Y=1.5-2 Medications OFF | Experimental | Same as above described Receives: Drug: PD patients H&Y=1.5-2 Medications OFF |
| PD patients H&Y=3 Medications OFF | Experimental | Same as above described Receives: Drug: PD patients H&Y=3 Medications OFF |
| Healthy age-matched controls | Experimental | Healthy controls. Right-handed healthy subjects (it will be assessed by the Edinburgh handedness inventory) with normal or corrected-to-normal vision, without a history of neurological diseases. Age range: 40-70. Receives: Behavioral: Healthy age-matched controls |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes of length of the Stop Signal Reaction Time
Reactive inhibition refers to the ability of a subject to react to the stop instruction, and it is measured by the stop-signal reaction time (SSRT). This variable cannot be measured, but it can be estimated by using the race model (21, 4, 16, 17, 18, 22).
Measured: Up to one year
Changes of the length of Reaction Times and Movement Times
Proactive inhibition refers to the ability of subjects to shape their response strategy in anticipation of known task demands driven by endogenous signals. In the case of the countermanding task, the endogenous signal is represented by the awareness of the fact that sometimes an imperative stop-signal could have been presented. Proactive control could be assessed by measuring reaction times (i.e. the time to initiate a response, RTs) and movement times (i.e. the time to execute the motor response, MTs) of no-stop trials. Previous research has shown that when a movement is produced in the context of the countermanding task, that is when the subject executes a no-stop trial, its RT is lengthened (e.g. 4, 15, 16, 17, 18, 22) and its MT is shortened compared to situations in which the same movement has to be performed in the context of a simple RT-task (go-only trial; 4, 15, 17)
Measured: Up to one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2018
- Study start30 Sep 2020
- Primary completion20 Jan 2023
- Study completion10 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for Idiopathic Parkinson's DiseaseStudies 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Model description
- Both groups of patients will perform the stop-signal task and the go-only task under two conditions: a) ON Levodopa medication state calculated after the first-morning dose which normally allowed the patient to attain the best control of symptoms (4) b) OFF Levodopa medication state. i.e patients did not take medications overnight prior to the study (19). Experimental conditions will be counterbalanced across patients and administered in two different experimental sessions occurring on different days. Healthy controls will perform the stop signal task and the go-only task in the same day. The order of administration will be counterbalanced.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Giovanni Mirabella
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Giovanni Mirabella, Neuromed IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03665493
- Sponsor's protocol ID
- GMirab_01
- Acronym
- DEI
- Status last verified
- Nov 2023
- First submitted
- 4 Sep 2018
- Last updated
- 18 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Mirabella G. Should I stay or should I go? Conceptual underpinnings of goal-directed actions. Front Syst Neurosci. 2014 Nov 3;8:206. doi: 10.3389/fnsys.2014.00206. eCollection 2014.
PubMed 25404898Mirabella G, Lebedev Mcapital A, Cyrillic. Interfacing to the brain's motor decisions. J Neurophysiol. 2017 Mar 1;117(3):1305-1319. doi: 10.1152/jn.00051.2016. Epub 2016 Dec 21.
PubMed 28003406Gauggel S, Rieger M, Feghoff TA. Inhibition of ongoing responses in patients with Parkinson's disease. J Neurol Neurosurg Psychiatry. 2004 Apr;75(4):539-44. doi: 10.1136/jnnp.2003.016469.
PubMed 15026491Mirabella G, Fragola M, Giannini G, Modugno N, Lakens D. Inhibitory control is not lateralized in Parkinson's patients. Neuropsychologia. 2017 Jul 28;102:177-189. doi: 10.1016/j.neuropsychologia.2017.06.025. Epub 2017 Jun 22.
PubMed 28647437Obeso I, Wilkinson L, Jahanshahi M. Levodopa medication does not influence motor inhibition or conflict resolution in a conditional stop-signal task in Parkinson's disease. Exp Brain Res. 2011 Sep;213(4):435-45. doi: 10.1007/s00221-011-2793-x. Epub 2011 Jul 28.
PubMed 21796541Claassen DO, van den Wildenberg WP, Harrison MB, van Wouwe NC, Kanoff K, Neimat JS, Wylie SA. Proficient motor impulse control in Parkinson disease patients with impulsive and compulsive behaviors. Pharmacol Biochem Behav. 2015 Feb;129:19-25. doi: 10.1016/j.pbb.2014.11.017. Epub 2014 Nov 29.
PubMed 25459105George JS, Strunk J, Mak-McCully R, Houser M, Poizner H, Aron AR. Dopaminergic therapy in Parkinson's disease decreases cortical beta band coherence in the resting state and increases cortical beta band power during executive control. Neuroimage Clin. 2013 Aug 8;3:261-70. doi: 10.1016/j.nicl.2013.07.013. eCollection 2013.
PubMed 24273711Wylie SA, van Wouwe NC, Godfrey SG, Bissett PG, Logan GD, Kanoff KE, Claassen DO, Neimat JS, van den Wildenberg WPM. Dopaminergic medication shifts the balance between going and stopping in Parkinson's disease. Neuropsychologia. 2018 Jan 31;109:262-269. doi: 10.1016/j.neuropsychologia.2017.12.032. Epub 2017 Dec 19.
PubMed 29269306Ghahremani DG, Lee B, Robertson CL, Tabibnia G, Morgan AT, De Shetler N, Brown AK, Monterosso JR, Aron AR, Mandelkern MA, Poldrack RA, London ED. Striatal dopamine D(2)/D(3) receptors mediate response inhibition and related activity in frontostriatal neural circuitry in humans. J Neurosci. 2012 May 23;32(21):7316-24. doi: 10.1523/JNEUROSCI.4284-11.2012.
PubMed 22623677Robertson CL, Ishibashi K, Mandelkern MA, Brown AK, Ghahremani DG, Sabb F, Bilder R, Cannon T, Borg J, London ED. Striatal D1- and D2-type dopamine receptors are linked to motor response inhibition in human subjects. J Neurosci. 2015 Apr 15;35(15):5990-7. doi: 10.1523/JNEUROSCI.4850-14.2015.
PubMed 25878272Albrecht DS, Kareken DA, Christian BT, Dzemidzic M, Yoder KK. Cortical dopamine release during a behavioral response inhibition task. Synapse. 2014 Jun;68(6):266-74. doi: 10.1002/syn.21736. Epub 2014 Feb 28.
PubMed 24677429Costa A, Peppe A, Mazzu I, Longarzo M, Caltagirone C, Carlesimo GA. Dopamine treatment and cognitive functioning in individuals with Parkinson's disease: the "cognitive flexibility" hypothesis seems to work. Behav Neurol. 2014;2014:260896. doi: 10.1155/2014/260896. Epub 2014 Jan 30.
PubMed 24825952van Wouwe NC, Kanoff KE, Claassen DO, Spears CA, Neimat J, van den Wildenberg WP, Wylie SA. Dissociable Effects of Dopamine on the Initial Capture and the Reactive Inhibition of Impulsive Actions in Parkinson's Disease. J Cogn Neurosci. 2016 May;28(5):710-23. doi: 10.1162/jocn_a_00930. Epub 2016 Feb 2.
PubMed 26836515Manza P, Amandola M, Tatineni V, Li CR, Leung HC. Response inhibition in Parkinson's disease: a meta-analysis of dopaminergic medication and disease duration effects. NPJ Parkinsons Dis. 2017 Jul 7;3:23. doi: 10.1038/s41531-017-0024-2. eCollection 2017.
PubMed 28702504Mirabella G, Iaconelli S, Modugno N, Giannini G, Lena F, Cantore G. Stimulation of subthalamic nuclei restores a near normal planning strategy in Parkinson's patients. PLoS One. 2013 May 3;8(5):e62793. doi: 10.1371/journal.pone.0062793. Print 2013.
PubMed 23658775
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dopamine Effect on Inhibitory Control
- ClinicalTrials.gov ID
- NCT03665493
- Acronym / sponsor ID
- DEI / GMirab_01
- Conditions
- Idiopathic Parkinson's Disease
- Keywords
- Levodopa medication, stop signal task, inhibitory control, Parkinson's Disease, stop signal reaction time, proactive inhibition
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Giovanni MirabellaUniversity, hospital or other
- Study start
- 30 Sep 2020 (actual)
- Primary completion
- 20 Jan 2023 (actual)
- Study completion
- 10 Nov 2023 (actual)
- First posted
- 11 Sep 2018 (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 effect of Levodopa medication on inhibitory control in Parkinson's patients is extremely debated despite the fact that this has potential clinical and therapeutic implications. A key confounding factor of many previous studies is that they did not take the disease duration in consideration. In fact, in moderate-to-advanced stages of Parkinson dopaminergic drugs could not produce a clear effect because too few dopaminergic cells for the drugs to operate on survived. Hence, in this study, we will compare the performance in the stop signal task in early-stage versus moderate-to-advanced stages Parkinson's patients both in ON and in OFF medication. In addition, to have a baseline measure of inhibitory control we will compare patient's performances with that of age-matched subjects.
Detailed description
The ability to stop a pending action is fundamental for survival in a natural environment where events cannot be fully predicted. Sudden events, such as the appearance of a physical obstacle, often require a quick change of the planned motor strategy and the first step toward this goal is to suppress the pre-programmed actions. Thus voluntary inhibition plays a crucial role in cognitive control and behavioral flexibility (1, 2). It has been shown that Parkinson's patients suffer from a specific deficit in this functions (3, 4, 5). However, it is extremely debated whether and how Levodopa medication (levodopa, dopamine agonists, anticholinergic drugs, or a combination of levodopa and an anticholinergic drug) affects response inhibition. A number of studies measuring inhibitory control via the stop signal task in Parkinson's patients seem to indicate that dopaminergic medications do not influence this executive function (5, 6, 7). However, a recent study (8) found that Levodopa medication does not affect specifically inhibitory control or movement readiness, but the balance between them. In fact, Parkinson's patients in the OFF medication state were able to maintain response latencies in the same range as healthy controls, but they showed a significant reduction in the ability to stop reactions abruptly. In contrast, patients' performance shifted significantly when taking dopaminergic medications. They move slower but stopping improved relative to the off dopamine state. This pattern suggests a role for dopamine in modulating the tradeoff between the two action control processes. In addition, studies of other specific populations and healthy adults suggest that dopaminergic medications deserve reconsideration in response inhibition. For instance, positron emission (PET) studies have found that higher levels of striatal D1 and D2/D3 receptor availability predict better performance on the stop signal task (9, 10) and that response inhibition performance evokes dopamine release in prefrontal, parietal, and temporal cortex in healthy adults (11). Even more importantly, a few recent studies provided evidence that early-stage Parkinson's patients with response inhibition impairment seem to benefit from dopaminergic treatment (12,13). Therefore, a plausible hypothesis is that the absence of a clear effect of dopaminergic medications could be ascribed to the fact that in most previous studies included Parkinson's patients in the moderate-to-advanced stages. In those patients, the diminished efficacy of dopaminergic drugs could be a consequence that too few dopaminergic cells for the drugs to operate on survived (14).
Hence, the aim of the present work is to re-assess the impact of dopaminergic medications on inhibitory control on Parkinson's patients using a reaching version of the stop signal task (e.g. 4, 15, 16, 17, 18) taking the disease duration in consideration. To this aim, the investigators will compare the performance in the stop signal task in early-stage versus moderate-to-advanced stages Parkinson's patients both in ON and in OFF medication. Finally, to have a baseline measure of inhibitory control the investigators will compare patients' performances with those of age-matched subjects.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 5
- Model description
- Both groups of patients will perform the stop-signal task and the go-only task under two conditions: a) ON Levodopa medication state calculated after the first-morning dose which normally allowed the patient to attain the best control of symptoms (4) b) OFF Levodopa medication state. i.e patients did not take medications overnight prior to the study (19). Experimental conditions will be counterbalanced across patients and administered in two different experimental sessions occurring on different days. Healthy controls will perform the stop signal task and the go-only task in the same day. The order of administration will be counterbalanced.
| Arm | Type | Receives |
|---|---|---|
| PD patients H&Y=1.5-2 Medications ON | Experimental | Drug: PD patients H&Y=1.5-2 Medications ONIdiopathic Parkinson's patient's with Hoehn and Yahr score of 1.5- 2 i.e. in an early stage of the disease, under stable treatment with the administration of L-dopa and dopamine agonists. Patients will not present severe sensory deficits or any other neurological disease besides PD, as will be assessed by a standard neurological examination, and they will be all right-handed as will be assessed by the Edinburgh handedness inventory. Age range: 40-70 |
| PD patients H&Y=3 Medications ON | Experimental | Drug: PD patients H&Y=3 Medications ONParkinson's patient's with Hoehn and Yahr score of 3, i.e. in moderate-to-advanced stages of the disease under stable treatment with the administration of L-dopa and dopamine agonists. Patients will not present severe sensory deficits or any other neurological disease besides PD, as will be assessed by a standard neurological examination, and they will be all right-handed as will be assessed by the Edinburgh handedness inventory. Age range: 40-70 |
| PD patients H&Y=1.5-2 Medications OFF | Experimental | Drug: PD patients H&Y=1.5-2 Medications OFFSame as above described |
| PD patients H&Y=3 Medications OFF | Experimental | Drug: PD patients H&Y=3 Medications OFFSame as above described |
| Healthy age-matched controls | Experimental | Behavioral: Healthy age-matched controlsHealthy controls. Right-handed healthy subjects (it will be assessed by the Edinburgh handedness inventory) with normal or corrected-to-normal vision, without a history of neurological diseases. Age range: 40-70. |
Who may qualify
- Ages
- 40 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Right-handedness (as assessed by the Edinburgh Handedness Inventory)
- Being in stable treatment with the administration of L-dopa and dopamine agonists (i.e. not having motor fluctuations and/or dyskinesia)
- Having a Hoehn \& Yahr score between 1.5 and 3
Key exclusion criteria (4 listed)
- Presence of severe sensory deficits
- Presence of overt signs of dementia (a. mini-mental state examination, MMSE must be ≥24; b. intelligence quotient ≥75).
- Comorbidity with other psychiatric disorders that might interfere with task execution (i.e. attentional disorders).
- Presence of severe tremor or rigidity of the right arm in the OFF medication state.
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 |
|---|---|---|
| PD patients H&Y=1.5-2 Medications ONParkinson's patients will be allowed to the first-morning dose of levodopa medicament (levodopa, dopamine agonists, anticholinergic drugs, or a combination of levodopa and an anticholinergic drug) which normally allowed the patient to attain the best control of symptoms one hour before being tested (19). Patients will perform both the stop-signal task and the go-only task. Experimental conditions will be counterbalanced across patients. | Drug | PD patients H&Y=1.5-2 Medications ON |
| PD patients H&Y=1.5-2 Medications OFFParkinson's patients will not take medications overnight prior to the study (20). Patients will perform both the stop-signal task and the go-only task. Experimental conditions will be counterbalanced across patients. This intervention will be given on a different day with respect to the Medication ON intervention. The order of intervention will be counterbalanced across subjects | Drug | PD patients H&Y=1.5-2 Medications OFF |
| Healthy age-matched controlsHealthy controls will perform the stop signal task and the go-only task in the same day. The order of administration will be counterbalanced. | Behavioural | Healthy age-matched controls |
| PD patients H&Y=3 Medications OFFParkinson's patients will not take medications overnight prior to the study (20). Patients will perform both the stop-signal task and the go-only task. Experimental conditions will be counterbalanced across patients. This intervention will be given on a different day with respect to the Medication ON intervention. The order of intervention will be counterbalanced across subjects | Drug | PD patients H&Y=3 Medications OFF |
| PD patients H&Y=3 Medications ONParkinson's patients will be allowed to the first-morning dose of levodopa medicament (levodopa, dopamine agonists, anticholinergic drugs, or a combination of levodopa and an anticholinergic drug) which normally allowed the patient to attain the best control of symptoms one hour before being tested (19). Patients will perform both the stop-signal task and the go-only task. Experimental conditions will be counterbalanced across patients. | Drug | PD patients H&Y=3 Medications ON |
Primary outcome
Changes of length of the Stop Signal Reaction Time
Time frame: Up to one year
Reactive inhibition refers to the ability of a subject to react to the stop instruction, and it is measured by the stop-signal reaction time (SSRT). This variable cannot be measured, but it can be estimated by using the race model (21, 4, 16, 17, 18, 22).
Changes of the length of Reaction Times and Movement Times
Time frame: Up to one year
Proactive inhibition refers to the ability of subjects to shape their response strategy in anticipation of known task demands driven by endogenous signals. In the case of the countermanding task, the endogenous signal is represented by the awareness of the fact that sometimes an imperative stop-signal could have been presented. Proactive control could be assessed by measuring reaction times (i.e. the time to initiate a response, RTs) and movement times (i.e. the time to execute the motor response, MTs) of no-stop trials. Previous research has shown that when a movement is produced in the context of the countermanding task, that is when the subject executes a no-stop trial, its RT is lengthened (e.g. 4, 15, 16, 17, 18, 22) and its MT is shortened compared to situations in which the same movement has to be performed in the context of a simple RT-task (go-only trial; 4, 15, 17)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2023.
- Background: PubMed 25404898Mirabella G. Should I stay or should I go? Conceptual underpinnings of goal-directed actions. Front Syst Neurosci. 2014 Nov 3;8:206. doi: 10.3389/fnsys.2014.00206. eCollection 2014.
- Background: PubMed 28003406Mirabella G, Lebedev Mcapital A, Cyrillic. Interfacing to the brain's motor decisions. J Neurophysiol. 2017 Mar 1;117(3):1305-1319. doi: 10.1152/jn.00051.2016. Epub 2016 Dec 21.
- Results publication: PubMed 15026491Gauggel S, Rieger M, Feghoff TA. Inhibition of ongoing responses in patients with Parkinson's disease. J Neurol Neurosurg Psychiatry. 2004 Apr;75(4):539-44. doi: 10.1136/jnnp.2003.016469.
- Results publication: PubMed 28647437Mirabella G, Fragola M, Giannini G, Modugno N, Lakens D. Inhibitory control is not lateralized in Parkinson's patients. Neuropsychologia. 2017 Jul 28;102:177-189. doi: 10.1016/j.neuropsychologia.2017.06.025. Epub 2017 Jun 22.
- Results publication: PubMed 21796541Obeso I, Wilkinson L, Jahanshahi M. Levodopa medication does not influence motor inhibition or conflict resolution in a conditional stop-signal task in Parkinson's disease. Exp Brain Res. 2011 Sep;213(4):435-45. doi: 10.1007/s00221-011-2793-x. Epub 2011 Jul 28.
- Results publication: PubMed 25459105Claassen DO, van den Wildenberg WP, Harrison MB, van Wouwe NC, Kanoff K, Neimat JS, Wylie SA. Proficient motor impulse control in Parkinson disease patients with impulsive and compulsive behaviors. Pharmacol Biochem Behav. 2015 Feb;129:19-25. doi: 10.1016/j.pbb.2014.11.017. Epub 2014 Nov 29.
- Results publication: PubMed 24273711George JS, Strunk J, Mak-McCully R, Houser M, Poizner H, Aron AR. Dopaminergic therapy in Parkinson's disease decreases cortical beta band coherence in the resting state and increases cortical beta band power during executive control. Neuroimage Clin. 2013 Aug 8;3:261-70. doi: 10.1016/j.nicl.2013.07.013. eCollection 2013.
- Results publication: PubMed 29269306Wylie SA, van Wouwe NC, Godfrey SG, Bissett PG, Logan GD, Kanoff KE, Claassen DO, Neimat JS, van den Wildenberg WPM. Dopaminergic medication shifts the balance between going and stopping in Parkinson's disease. Neuropsychologia. 2018 Jan 31;109:262-269. doi: 10.1016/j.neuropsychologia.2017.12.032. Epub 2017 Dec 19.
- Results publication: PubMed 22623677Ghahremani DG, Lee B, Robertson CL, Tabibnia G, Morgan AT, De Shetler N, Brown AK, Monterosso JR, Aron AR, Mandelkern MA, Poldrack RA, London ED. Striatal dopamine D(2)/D(3) receptors mediate response inhibition and related activity in frontostriatal neural circuitry in humans. J Neurosci. 2012 May 23;32(21):7316-24. doi: 10.1523/JNEUROSCI.4284-11.2012.
- Results publication: PubMed 25878272Robertson CL, Ishibashi K, Mandelkern MA, Brown AK, Ghahremani DG, Sabb F, Bilder R, Cannon T, Borg J, London ED. Striatal D1- and D2-type dopamine receptors are linked to motor response inhibition in human subjects. J Neurosci. 2015 Apr 15;35(15):5990-7. doi: 10.1523/JNEUROSCI.4850-14.2015.
- Results publication: PubMed 24677429Albrecht DS, Kareken DA, Christian BT, Dzemidzic M, Yoder KK. Cortical dopamine release during a behavioral response inhibition task. Synapse. 2014 Jun;68(6):266-74. doi: 10.1002/syn.21736. Epub 2014 Feb 28.
- Results publication: PubMed 24825952Costa A, Peppe A, Mazzu I, Longarzo M, Caltagirone C, Carlesimo GA. Dopamine treatment and cognitive functioning in individuals with Parkinson's disease: the "cognitive flexibility" hypothesis seems to work. Behav Neurol. 2014;2014:260896. doi: 10.1155/2014/260896. Epub 2014 Jan 30.
- Individual participant dataSharing planned: Undecided
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing PD patients H&Y=1.5-2 Medications ON, PD patients H&Y=1.5-2 Medications OFF and PD patients H&Y=3 Medications OFF in people with Idiopathic Parkinson's Disease, run by Giovanni Mirabella at 1 site in Italy.
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 3 inclusion and 4 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 18 Nov 2023. 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 Italy. 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. 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?
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 of length of the Stop Signal Reaction Time (time frame: Up to one year). 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 NCT03665493, which also lists 22 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 18 Nov 2023.