Efficacy of a Prediction Model-based Algorithm to PREVENT Drug-induced Impulse Control Disorders in Parkinson's Disease (PREVENT-ICD)

Impulse control disorders and related behaviors (ICDRBs) are characterized by pathological gambling, compulsive shopping or eating, and hypersexuality, but other related behaviors have been described, e.g. hobbyism, and punding. ICDRBs are frequent in Parkinson's Disease (PD), affecting up to 50% of the patients after 5 years with major medical, social, and legal impact, with life changing consequences for patients and caregivers. The main risk factor is dopaminergic therapy, particularly the cumulative dose of dopamine agonists (DA). On the other hand, the dopaminergic therapy is necessary to control motor symptoms, and DA have demonstrated efficacy in delaying motor complications occurring in PD. Ideally, dopaminergic therapy would have to be adjusted to the individual risk of developing ICRDBs to maximize the benefit/risk ratio of each drug. However, despite several clinical risk factors associated with the risk of ICDRBs (in addition to the dopaminergic therapy), it is still not possible to predict their risk at the individual level, and not every patient treated with dopaminergic medications will develop ICDRBs. A machine learning algorithm to predict ICDRBs, based on clinical data, validated by cross-validation on independent replication cohorts has been developed. The PREVENT-ICD study proposes to test the efficacy of a new application, ICD-Shield, based on an algorithm to predict and prevent ICDs,in a multicenter randomized controlled trial to prevent ICDRBs in PD patients by proposing to the clinician treatment adjustment according to the risk predicted by the algorithm, as compared to the standard of care (SoC)

Study Overview

• Status: Not yet recruiting
• Conditions: Parkinson Disease; Impulse Control Disorder
• Intervention / Treatment: Device: Algorithm-guided group; Behavioral: Standard of Care (SoC) group

Detailed Description

This Clinical Investigation is a multicenter comparative randomized, controlled, masked (patient and primary criteria evaluator), superiority trial, with 2 parallel groups (Intervention group: Algorithm-guided arm; Control group: standard of care arm).

PD patients, treated by DA at inclusion, will be randomized (1:1 ratio) either to the standard of care (SoC) arm, or to the Algorithm-guided arm. They will be recruited at PD expert centers of the NSPARK/FCRIN network. The primary objective is to assess the efficacy of the ICD SHIELD app, a software with a computer-based algorithm assisting clinicians in the prescription of dopaminergic medications, as compared to the standard of care, on the primary endpoint After the inclusion (V0 at M0), four follow-up visits will be performed : V1 at M6, V2 at M12, V3 at M18 and V4 at M24 during outpatients clinics where participants are usually followed. At each follow up visit (M6 to M24), the neurologist will record medical and treatment history, perform neurological examination MDS-UPDRS sections III to IV and CGI-I scale, and will review the MDS-UPDRS sections I and II for potential reassessment/clarification. The PGI scale, PDQ39 questionnaire, MDS-UPDRS sections I and II, and the HAD scales will be filled by the patient. The MoCA scale, ASBPD and QUIP-RS will be performed by a neuropsychologist, or an investigator trained for each scale, according to scoring instructions and blind to treatment arm allocation. Then, the treatment will be adapted by the neurologist, according to the recommendation by the algorithm output or to the clinician sole recommendation depending on the arm in which the patient is randomized.

An additional phone call will be made 3 months after the previous visit for a remote checkup to confirm that the prescription change (decreasing or stopping DA) has been properly followed by the patient, if the adjustment to stop completely or decrease DA to a dose equivalent of 40mg of Levodopa was applied.

An optional blood sample will be drawn at baseline or at a follow-up visit and sent for DNA extraction and biobanking at the ICM, Pitié-Salpêtrière Hospital, Paris. The duration of recruitment will be 2 years. The duration of participation for each participant will be 2 years, the total duration of the study will be 4 years.

The main analysis will be in Intention to treat and will involve a mixed generalized linear model (GLMM) with a logit link adjusted for minimization stratification factors (center, sex, age, Levodopa Equivalent Daily Dose (LEDD) at inclusion).

• Study Type: Interventional
• Enrollment (Estimated): 528
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sofia Zemouri, Master; Phone Number: 01 42 16 75 75; Email: sofia.zemouri@aphp.fr
• Study Contact Backup: Name: Louise-Laure Mariani, Doctor; Phone Number: 01 42 16 27 48; Email: louise-laure.mariani@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male and female ≥ 18 years old
• Diagnosis of PD according to the 2015 Movement Disorders Society criteria (Postuma et al., Mov Disord. 2015), with bradykinesia AND at least ONE of the following: muscular rigidity, or resting tremor; with no other suspected cause of parkinsonism
• Disease duration below 6 years included
• No ongoing clinically significant (Mild or above) ICDRBs (ASBPD part IV subscores each <2)
• Patients currently treated with DA for at least 2 months and without current planned or known reason for stopping DA over the next 2 years

Exclusion Criteria:

• Atypical or secondary parkinsonism such as supranuclear palsy, multisystem atrophy or drug-induced parkinsonism, etc...

  • Patients with a cognitive or psychiatric disorder preventing patient's participation as per investigator's judgement
  • Not willing to participate to the Clinical Investigation or to sign the consent
  • Pregnant or lactating woman, or WOCBP tested positive in <serum or urine> pregnancy test
  • Participation in investigational drug trials within 30 days prior to screening or within 5 half-life of investigational product whatever the longest
  • Participant not affiliated or beneficiary of a French social security system

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Algorithm-guided group; In the (algorithm-guided arm) the patient treatment will be adapted by the neurologist based on the algorithm output.	Device: Algorithm-guided group; After the evaluation of the patient and the clinical inputs entered in the ICD SHIELD app including the planned choice of prescription by the neurologist for the next period, the clinician will receive the therapeutic approach recommended by the ICD SHIELD app depending on the output given by the algorithm. The clinician can repeat the use of the app if he/she plans to try various choice of prescription in the app if deemed necessary, but a single use is recommended at each visit. The neurologist will have to follow the recommendation of the ICD SHIELD app as much as possible unless judged inappropriate. The neurologist makes the final decision.
Other: Standard of Care (SoC) group; In the SoC arm the patient treatment will be adapted by the neurologist based only on their clinical appreciation and international guidelines.	Behavioral: Standard of Care (SoC) group; In the SoC arm the patient treatment will be adapted by the neurologistbased only on their clinical appreciation and international guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of patients with at least one clinically significant ICDRBs, i.e mild or above (any ASBPD score at 2 or above in any of the subcategories 3 to 5 and 7 to 10 of part IV) over the 2 year-follow up.	ICDRBs will be screened for, every 6 months, with the internationally validated Ardouin Scale of Behavior in PD (ASBPD), according to scoring instructions, by a neuropsychologist or the neurologist trained for the scale. The diagnosis of a clinically significant ICDRB (MILD or above) relies on part IV of the ASBPD, hyperdopaminergic behaviors, for patients who score at 2 or above in any of the subcategories 3 to 5 and 7 to 10	over 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Perception of global disease severity by the patient	Change in disease severity of PD on the Patient Global Impression of Improvement (PGI-I) scale filled by the patient over the 2 year-long-follow up. The PGI is a Patient Global Impression 7-point scale that requires the rating of the severity of the patient's illness at the time of assessment. It is assessed by asking the patient at each visit which alternative described how they had felt during the last 7 days as compared to how they felt at the baseline observation. A higher value indicates increased improvement from Clinical Investigation start, ranging from 1=very much worse to 7=very much improved.	over 2 years
Perception of global disease severity by the clinician	Change in disease severity of PD on the Clinical Global Impression of Improvement (CGI-I) scale filled by the clinician over the 2 year-long-follow up. The Change in the Neurologist (clinician) Global Impression of Improvement (CGI-I) provides a brief, stand-alone assessment of the clinician's view of the patient's global functioning prior to and after initiating a study medication. The Clinical Global Impression-Improvement scale rates total improvement on a 7-point scale: 1= Very much improved; 2= Much improved; 3= Minimally improved; 4= No change; 5= Minimally worse; 6= Much worse; 7= Very much worse.	over 2 years
Time to onset of first occurrence of clinically significant ICDRBs	Time to onset of a first clinically significant ICDRBs, i.e mild or above, defined as any ASBPD score at 2 or above in any of the subcategories 3 to 5 and 7 to 10 of part IV over the 2 year-long-follow up.	over 2 years
Global severity of ICDRBs at time of first occurrence on the QUIP-RS score	Severity of ICDRBs at time of first occurrence assessed on the Questionnaire For Impulsive-Compulsive Disorders In Parkinson's Disease-Rating Scale (QUIP-RS) score (Score ranges from 0 to 112, a higher score reflecting a more severe ICDRB) over the 2 year-long-follow up.	over 2 years
Highest severity of ICDRBs at time of first occurrence on the ASBPD score	Severity of ICDRBs at time of first occurrence assessed on ASBPD score (highest severity on part IV of the ASBPD, hyperdopaminergic behaviors, in any of the subcategories 3 to 5 and 7 to 10) over the 2 year-long-follow up.	over 2 years
Global severity of ICDRBs at time of first occurrence on the ASBPD score	Global severity of ICDRBs at time of first occurrence assessed by the sum of ICDRBs items' scores on ASBPD (subcategories 3 to 5 and 7 to 10 of the part IV hyperdopaminergic behaviors) over the 2 year-long-follow up.	over 2 years
Cumulative levodopa equivalent daily dose (LEDD)	Intakes of dopaminergic medications will be calculated to an equivalent dose of levodopa allowing for standardized evaluation of medication intake among PD patients by expressing dose intensity of different antiparkinsonian drug regimens on a single scale ((Jost et al., 2023; Tomlinson et al., 2010). Cumulative LEDD will be assessed as the sum of the daily doses over the 2 year-follow up, recorded at each visit (M6, M12, M18, M24).	over 2 years
Time to first DA stopping	Time to onset of a first DA stopping, whatever the reason, over the 2 year-long-follow up.	over 2 years
Reasons for first DA stopping	Rate of each reasons given by the neurologist for the first DA stopping over the 2 year-long-follow up, among: clinically significant ICDRBs, other adverse event of DA than ICDRBs, risk of clinically significant ICDRBs as judged by the neurologist and/or the ICD SHIELD app, insufficient efficacy, other or unknown reason.	over 2 years
Motor control	Change in motor score on the MDS-UPDRS (MDS-UPDRS III sub-score) over the 2 year-long-follow up. Score between 0 and 132, a higher score reflects a more severe motor state. The MDS-UPDRS III sub-score is the gold standard for measuring the clinical motor state of PD patients.	over 2 years
Dyskinesia	Change in the dyskinesia score on the MDS-UPDRS (sum of MDS-UPDRS IV items 4.1 and 4.2) over the 2 years.	over 2 years
Motor fluctuation	Change in the motor fluctuations score on the MDS-UPDRS (sum of MDS-UPDRS IV items 4.3 to 4.6) over the 2 years.	over the 2 years.
Depression (MDS-UPDRS scale)	Change in depression score item 1.3 of the MDS-UPDRS scale over the 2 year-follow up	over 2 years
Depression (HADS subscore)	Change in HADS depression subscore over the 2 year-follow up. It comprises 14 items each ranging from 0 to 3. Seven questions are evaluating anxiety (total A) and seven others to depressive dimension (total D), obtaining two scores (maximal score = 21 for each). A higher value indicates increased anxiety (total A) or depression (total D).	over 2 years
Anxiety (MDS-UPDRS scale)	Change in anxiety score item 1.4 of the MDS-UPDRS scale over the 2 year-follow up	over 2 years
Anxiety (HADS subscore)	Change in HADS anxiety subscore over the 2 year-follow up. It comprises 14 items each ranging from 0 to 3. Seven questions are evaluating anxiety (total A) and seven others to depressive dimension (total D), obtaining two scores (maximal score = 21 for each). A higher value indicates increased anxiety (total A) or depression (total D).	over 2 years
Somnolence	Change in somnolence score item 1.8 of the MDS-UPDRS over the 2 year-follow up	over 2 years
Sleep disorders	Change in sleep issues score item 1.7 of the MDS-UPDRS over the 2 year-follow up	over 2 years
Apathy	Change in apathy score item 1.5 of the MDS-UPDRS scale over the 2 year-follow up	over 2 years
Cognition	Change in cognition MoCA scale over the 2 year-follow up. The MoCA is a 30-point cognitive screening instrument that assesses visuospatial, executive, naming, attention, language, abstraction, delayed recall, and orientation domains. A cutoff score of 26 is normative cognitive function.	over 2 years
Serious Adverse Events	Number, type and imputability of serious adverse events within a 2 year follow up period.	over 2 years
Observance of the ICD SHIELD app for clinicians	Percentage of visits in which the clinician decided not to follow ICD SHIELD app recommendation over the 2 year-follow up	over 2 years
Acceptability of the ICD SHIELD app for clinicians	Reasons for not following the ICD SHIELD app recommendation: a short open-ended questionnaire to assess the acceptability of the intervention. These open-ended questions will be analyzed qualitatively	over 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative severity of ICDRBs	Cumulative severity of ICDRBs within the 2-year period assessed by the sum of the QUIP-RS score at each visit (M6, M12, M18, M24)	over 2 years
Subtypes of ICDRBs	Change in each subtype of ICDRBs within the 2-year period assessed by each respective QUIP-RS sub-score (sub-scores A to G). Score ranges from 0 to 16 for each category. A higher score reflects a more severe ICD.	over 2 years
Patient quality of life	Change in the quality of life measured by PDQ-39 scale score over the 2 year-follow up. A higher score reflects a poorer quality of life.	over 2 years
Body weight change	Change in body weight (in kg, measured at each patient visit) over the 2 year-long-follow up	over 2 years
Cumulative dose of DA	Cumulative DA doses assessed by the sum of the daily doses over the 2 year-follow up	over 2 years
Cumulative dose of levodopa	Cumulative levodopa doses assessed by the sum of the daily doses over the 2 year-follow up	over 2 years
Cumulative dose of COMT inhibitors	Cumulative COMT inhibitors doses assessed by the sum of the daily doses over the 2 year-follow up	over 2 years
Cumulative dose of MAO-B inhibitors	Cumulative MAO-B inhibitors doses assessed by the sum of the daily doses over the 2 year-follow up,	over 2 years
Cumulative dose of anticholinergic treatments	Cumulative anticholinergic doses assessed by the sum of the daily doses over the 2 year-follow up,	over 2 years
Cumulative dose of amantadine treatments	Cumulative amantadine doses assessed by the sum of the daily doses over the 2 year-follow up.	over 2 years
Monthly LEDD	Change in monthly LEDD over the 2 years. Monthly LEDD calculated as the mean of the LEDD over each month.	over 2 years
Adverse events causing DA stopping or decrease	Rate of patient with a DA stopping or decrease for any other adverse events reason than ICD (lower limbs swelling, Excessive Daytime Sleepiness, fainting or dizziness due to orthostatic hypotension, hallucinations, …), as judged by the neurologist, over the 2 year-follow up	over 2 years
Occurrence of Dopamine Agonist Withdrawal Syndrome (DAWS)	Rate of patients with a DAWS over the 2 year-follow up. DAWS is defined as the occurrence or significant worsening of one or more nonmotor symptoms such as anxiety, panic attacks, depression, agitation, irritability, drug craving, insomnia, daytime fatigue, diaphoresis, nausea, vomiting, flushing, orthostasis, and generalized pain in the context of discontinuation or tapering of DA (Debove et al. 2024), as judged by the neurologist.	over 2 years
Additional unscheduled visits due to adverse events	Number of additional unscheduled visits due to adverse events to the neurologist over the 2 year-follow up.	over 2 years
Genetic standardized net benefit statistic	13 candidate variants selected from the DRD2, DRD3, DAT1, COMT, DDC, GRIN2B, ADRA2C, SERT, TPH2, HTR2A, OPRK1 and OPRM1 genes. In the standard of care arm, change in the standardized net benefit statistic, change in true positive rates, change in false positive rates, between the algorithm with and without genomic results, calculated at threshold that would be considered the most relevant for each algorithm	over 2 years

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: NS-PARK Network
• Investigators: Study Director: Louise-Laure Mariani, Assistance Publique Hopitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2030

Study Registration Dates

• First Submitted: March 26, 2026
• First Submitted That Met QC Criteria: March 26, 2026
• First Posted (Actual): April 1, 2026

Study Record Updates

• Last Update Posted (Actual): April 1, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Impulse Control Disorders; Agonists, Dopamine; ICD SHIELD app
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease; Disruptive, Impulse Control, and Conduct Disorders; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Population Characteristics; Demography; Standard of Care; Population Groups
• Other Study ID Numbers: APHP220831; 2024-A02552-45 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Data are available upon reasonable request to the Coordinating Principal Investigator/Corresponding author, and according to local regulations and depending on futur use of the medical device in case of CE mark and commercialization.

The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients.

Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.

• IPD Sharing Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor
• IPD Sharing Access Criteria: Researchers who provide a methodological sound proposal, with clearly identified processing purposes and subject to compliance with applicable regulations (CNIL, GDPR)
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No