Efficacy of a Prediction Model-based Algorithm to PREVENT Drug-induced Impulse Control Disorders in Parkinson's Disease
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 528
- 主要终点
- 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.
研究概览
简要总结
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)
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •* 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 \ 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
研究组 & 干预措施
Algorithm-guided group
In the (algorithm-guided arm) the patient treatment will be adapted by the neurologist based on the algorithm output.
干预措施: Algorithm-guided group (Device)
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.
干预措施: Standard of Care (SoC) group (Behavioral)
结局指标
主要结局
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.
时间窗: 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
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.
时间窗: over 2 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
次要结局
- Perception of global disease severity by the patient(over 3 years)
- Perception of global disease severity by the clinician(over 3 years)
- Time to onset of first occurrence of clinically significant ICDRBs(over 3 years)
- Global severity of ICDRBs at time of first occurrence on the QUIP-RS score(over 3 years)
- Highest severity of ICDRBs at time of first occurrence on the ASBPD score(over 3 years)
- Global severity of ICDRBs at time of first occurrence on the ASBPD score(over 3 years)
- Cumulative levodopa equivalent daily dose (LEDD)(over 3 years)
- Time to first DA stopping(over 3 years)
- Reasons for first DA stopping(over 3 years)
- Motor control(over 3 years)
- Dyskinesia(over 3 years)
- Motor fluctuation(over the 3 years.)
- Depression (MDS-UPDRS scale)(over 3 years)
- Depression (HADS subscore)(over 3 years)
- Anxiety (MDS-UPDRS scale)(over 3 years)
- Anxiety (HADS subscore)(over 3 years)
- Somnolence(over 3 years)
- Sleep disorders(over 3 years)
- Apathy(over 3 years)
- Cognition(over 3 years)
- Serious Adverse Events(over 3 years)
- Observance of the ICD SHIELD app for clinicians(over 3 years)
- Acceptability of the ICD SHIELD app for clinicians(over 3 years)
- Perception of global disease severity by the patient(over 2 years)
- Perception of global disease severity by the clinician(over 2 years)
- Time to onset of first occurrence of clinically significant ICDRBs(over 2 years)
- Global severity of ICDRBs at time of first occurrence on the QUIP-RS score(over 2 years)
- Highest severity of ICDRBs at time of first occurrence on the ASBPD score(over 2 years)
- Global severity of ICDRBs at time of first occurrence on the ASBPD score(over 2 years)
- Cumulative levodopa equivalent daily dose (LEDD)(over 2 years)
- Time to first DA stopping(over 2 years)
- Reasons for first DA stopping(over 2 years)
- Motor control(over 2 years)
- Dyskinesia(over 2 years)
- Motor fluctuation(over the 2 years.)
- Depression (MDS-UPDRS scale)(over 2 years)
- Depression (HADS subscore)(over 2 years)
- Anxiety (MDS-UPDRS scale)(over 2 years)
- Anxiety (HADS subscore)(over 2 years)
- Somnolence(over 2 years)
- Sleep disorders(over 2 years)
- Apathy(over 2 years)
- Cognition(over 2 years)
- Serious Adverse Events(over 2 years)
- Observance of the ICD SHIELD app for clinicians(over 2 years)
- Acceptability of the ICD SHIELD app for clinicians(over 2 years)