Impulse Control Disorder, Parkinson Disease
Conditions
Keywords
Agonists, Dopamine, Impulse Control Disorders, ICD SHIELD app
Brief summary
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)
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 M9, V2 at M18, V3 at M27 and V4 at M36 during outpatients clinics where participants are usually followed. At each follow up visit (M9 to M36), 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 3 years, the total duration of the study will be 5 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).
Interventions
DEVICEAlgorithm-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.
BEHAVIORALStandard 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.
Sponsors
Assistance Publique - Hôpitaux de Paris
NS-PARK Network
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 (any ASBPD part IV subscores in any of the items 3 to 5 and 7 to 10 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 3 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 3 year-follow up. | over 3 years | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Perception of global disease severity by the patient | over 3 years | Change in disease severity of PD on the Patient Global Impression of Improvement (PGI-I) scale filled by the patient over the 3 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. |
| Perception of global disease severity by the clinician | over 3 years | Change in disease severity of PD on the Clinical Global Impression of Improvement (CGI-I) scale filled by the clinician over the 3 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. |
| Time to onset of first occurrence of clinically significant ICDRBs | over 3 years | 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 3 year-long-follow up. |
| Global severity of ICDRBs at time of first occurrence on the QUIP-RS score | over 3 years | 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 3 year-long-follow up. |
| Highest severity of ICDRBs at time of first occurrence on the ASBPD score | over 3 years | 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 3 year-long-follow up. |
| Global severity of ICDRBs at time of first occurrence on the ASBPD score | over 3 years | 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 3 year-long-follow up. |
| Cumulative levodopa equivalent daily dose (LEDD) | over 3 years | 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 3 year-follow up, recorded at each visit (M9 M18, M27, M36). |
| Time to first DA stopping | over 3 years | Time to onset of a first DA stopping, whatever the reason, over the 3 year-long-follow up. |
| Reasons for first DA stopping | over 3 years | Rate of each reasons given by the neurologist for the first DA stopping over the 3 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. |
| Motor control | over 3 years | Change in motor score on the MDS-UPDRS (MDS-UPDRS III sub-score) over the 3 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. |
| Dyskinesia | over 3 years | Change in the dyskinesia score on the MDS-UPDRS (sum of MDS-UPDRS IV items 4.1 and 4.2) over the 3 years. |
| Motor fluctuation | over the 3 years. | Change in the motor fluctuations score on the MDS-UPDRS (sum of MDS-UPDRS IV items 4.3 to 4.6) over the 3 years. |
| Depression (MDS-UPDRS scale) | over 3 years | Change in depression score item 1.3 of the MDS-UPDRS scale over the 3 year-follow up |
| Depression (HADS subscore) | over 3 years | Change in HADS depression subscore over the 3 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). |
| Anxiety (MDS-UPDRS scale) | over 3 years | Change in anxiety score item 1.4 of the MDS-UPDRS scale over the 3 year-follow up |
| Anxiety (HADS subscore) | over 3 years | Change in HADS anxiety subscore over the 3 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). |
| Somnolence | over 3 years | Change in somnolence score item 1.8 of the MDS-UPDRS over the 3 year-follow up |
| Sleep disorders | over 3 years | Change in sleep issues score item 1.7 of the MDS-UPDRS over the 3 year-follow up |
| Apathy | over 3 years | Change in apathy score item 1.5 of the MDS-UPDRS scale over the 3 year-follow up |
| Cognition | over 3 years | Change in cognition MoCA scale over the 3 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. |
| Serious Adverse Events | over 3 years | Number, type and imputability of serious adverse events within a 3 year follow up period. |
| Observance of the ICD SHIELD app for clinicians | over 3 years | Percentage of visits in which the clinician decided not to follow ICD SHIELD app recommendation over the 3 year-follow up |
| Acceptability of the ICD SHIELD app for clinicians | over 3 years | 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 |
Contacts
CONTACTLouise-Laure Mariani, Doctor
CONTACTSofia Zemouri, Master
STUDY_DIRECTORLouise-Laure Mariani
Assistance Publique - Hôpitaux de Paris
Outcome results
None listed