NCT03665493

Brief 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. 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
90

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started Sep 2020

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 4, 2018

Completed
7 days until next milestone

First Posted

Study publicly available on registry

September 11, 2018

Completed
2.1 years until next milestone

Study Start

First participant enrolled

September 30, 2020

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 20, 2023

Completed
10 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 10, 2023

Completed
Last Updated

November 18, 2023

Status Verified

November 1, 2023

Enrollment Period

2.3 years

First QC Date

September 4, 2018

Last Update Submit

November 15, 2023

Conditions

Idiopathic Parkinson's Disease

Keywords

Levodopa medicationstop signal taskinhibitory controlParkinson's Diseasestop signal reaction timeproactive inhibition

Outcome Measures

Primary Outcomes (2)

  • 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).

    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)

    Up to one year

Study Arms (5)

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

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

Drug: PD patients H&Y=3 Medications ON

PD patients H&Y=1.5-2 Medications OFF

EXPERIMENTAL

Same as above described

Drug: PD patients H&Y=1.5-2 Medications OFF

PD patients H&Y=3 Medications OFF

EXPERIMENTAL

Same as above described

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.

Behavioral: Healthy age-matched controls

Interventions

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 ON
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

PD patients H&Y=1.5-2 Medications OFF
Healthy age-matched controlsBEHAVIORAL

Healthy controls will perform the stop signal task and the go-only task in the same day. The order of administration will be counterbalanced.

Healthy age-matched controls
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 OFF
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.

PD patients H&Y=3 Medications ON

Eligibility Criteria

Age40 Years - 70 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

IRCSS Neuromed Hospital

Pozzilli, Isernia, 86077, Italy

Location

Related Publications (22)

  • 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.

    PMID: 25404898BACKGROUND

  • Mirabella 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.

    PMID: 28003406BACKGROUND

  • Gauggel 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.

    PMID: 15026491RESULT

  • Mirabella 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.

    PMID: 28647437RESULT

  • Obeso 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.

    PMID: 21796541RESULT

  • Claassen 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.

    PMID: 25459105RESULT

  • George 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.

    PMID: 24273711RESULT

  • Wylie 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.

    PMID: 29269306RESULT

  • Ghahremani 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.

    PMID: 22623677RESULT

  • Robertson 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.

    PMID: 25878272RESULT

  • Albrecht 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.

    PMID: 24677429RESULT

  • Costa 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.

    PMID: 24825952RESULT

  • van 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.

    PMID: 26836515RESULT

  • Manza 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.

    PMID: 28702504RESULT

  • Mirabella 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.

    PMID: 23658775RESULT

  • Mirabella G, Iaconelli S, Romanelli P, Modugno N, Lena F, Manfredi M, Cantore G. Deep brain stimulation of subthalamic nuclei affects arm response inhibition in Parkinson's patients. Cereb Cortex. 2012 May;22(5):1124-32. doi: 10.1093/cercor/bhr187. Epub 2011 Aug 1.

    PMID: 21810782RESULT

  • Mirabella G, Pani P, Ferraina S. Context influences on the preparation and execution of reaching movements. Cogn Neuropsychol. 2008 Oct-Dec;25(7-8):996-1010. doi: 10.1080/02643290802003216.

    PMID: 19378414RESULT

  • Mirabella G, Pani P, Ferraina S. Neural correlates of cognitive control of reaching movements in the dorsal premotor cortex of rhesus monkeys. J Neurophysiol. 2011 Sep;106(3):1454-66. doi: 10.1152/jn.00995.2010. Epub 2011 Jun 22.

    PMID: 21697448RESULT

  • Mirabella G, De Vita P, Fragola M, Rampelli S, Lena F, Dilettuso F, Iacopini M, d'Avella R, Borgese MC, Mazzotta S, Lanni D, Grano M, Lubrani S, Modugno N. Theatre Is a Valid Add-On Therapeutic Intervention for Emotional Rehabilitation of Parkinson's Disease Patients. Parkinsons Dis. 2017;2017:7436725. doi: 10.1155/2017/7436725. Epub 2017 Nov 22.

    PMID: 29359066RESULT

  • Moro E, Scerrati M, Romito LM, Roselli R, Tonali P, Albanese A. Chronic subthalamic nucleus stimulation reduces medication requirements in Parkinson's disease. Neurology. 1999 Jul 13;53(1):85-90. doi: 10.1212/wnl.53.1.85.

    PMID: 10408541RESULT

  • Mirabella G, Pani P, Pare M, Ferraina S. Inhibitory control of reaching movements in humans. Exp Brain Res. 2006 Sep;174(2):240-55. doi: 10.1007/s00221-006-0456-0. Epub 2006 Apr 25.

    PMID: 16636792RESULT

  • Logan GD, Cowan WB, Davis KA. On the ability to inhibit simple and choice reaction time responses: a model and a method. J Exp Psychol Hum Percept Perform. 1984 Apr;10(2):276-91. doi: 10.1037//0096-1523.10.2.276.

    PMID: 6232345RESULT

MeSH Terms

Conditions

Parkinson DiseaseProactive Inhibition

Condition Hierarchy (Ancestors)

Parkinsonian DisordersBasal Ganglia DiseasesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesMovement DisordersSynucleinopathiesNeurodegenerative DiseasesInhibition, PsychologicalBehavior

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
Purpose
BASIC SCIENCE
Intervention Model
FACTORIAL
Model Details: 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.
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

September 4, 2018

First Posted

September 11, 2018

Study Start

September 30, 2020

Primary Completion

January 20, 2023

Study Completion

November 10, 2023

Last Updated

November 18, 2023

Record last verified: 2023-11

Locations

IT(1)