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

Обзор

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)

Подробное описание

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).

Вмешательства

• Устройство 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 neurologis
• Поведенческое 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.

Первичные конечные точки

• 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. [Срок оценки: over 3 years]

Вторичные конечные точки (12)

• Perception of global disease severity by the patient [Срок оценки: over 3 years]
• Perception of global disease severity by the clinician [Срок оценки: over 3 years]
• Time to onset of first occurrence of clinically significant ICDRBs [Срок оценки: over 3 years]
• Global severity of ICDRBs at time of first occurrence on the QUIP-RS score [Срок оценки: over 3 years]
• Highest severity of ICDRBs at time of first occurrence on the ASBPD score [Срок оценки: over 3 years]
• Global severity of ICDRBs at time of first occurrence on the ASBPD score [Срок оценки: over 3 years]
• Cumulative levodopa equivalent daily dose (LEDD) [Срок оценки: over 3 years]
• Time to first DA stopping [Срок оценки: over 3 years]
• Reasons for first DA stopping [Срок оценки: over 3 years]
• Motor control [Срок оценки: over 3 years]
• Dyskinesia [Срок оценки: over 3 years]
• Motor fluctuation [Срок оценки: over the 3 years.]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Профилактика

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07505394 · APHP220831 · 2024-A02552-45

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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