neuroQWERTY: a Transparent Patient-centered Outcome Method to Quantify Parkinsonian Motor Signs for Drug Trials

Completed

• Conditions: Parkinson Disease

• Registration Number: NCT02522065
• Lead Sponsor: Fundación de investigación HM

Brief Summary

The motor impairment produced by Parkinson's disease (PD) is a significant and debilitating part of the condition. Current methods to evaluate this impairment rely on subjective examinations. The investigators seek to develop an objective assessment of motor deficits by monitoring the participants natural interactions with a keyboard (on a computer or smart device). This approach provides a window to how the brain behaves during typical daily use of these devices, i.e. writing a report, sending an email or any other task performed on a digital device and thus has the potential to be used easily and regularly. (Importantly, the data gathered are non-sensitive and based only on timing information).

PD participants will be recruited during outpatient visits to PD clinics throughout the Madrid metropolitan region. General entry criteria will be those patients who are scheduled to begin dopaminergic therapy, and own a home computer or laptop. The study will not impact on participants' standard clinical management other than by asking the participants to type for 15 minutes at each of the clinic visits, and installing the investigators proprietary software on their home computer. This software will collect keystroke data alone. (None of the actual information about what is being typed will be collected.) The keystroke data collected will be analyzed and compared with standard clinical metrics of therapeutic response, as well as the in-clinic typing data.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-05
• Study First Submitted: 2015-08-06
• Study First Submitted QC: 2015-08-10
• Study First Posted: 2015-08-13
• Primary Completion: 2016-12
• Study Completion: 2016-12
• Status Verified: 2019-04
• Last Update Submitted: 2019-04-02
• Last Update Posted: 2019-04-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Participants between 18 years and 70 years (older subjects will be deemed eligible on an individual basis after review by the study team).

2. Parkinson's disease (PD) diagnosis according to the United Kingdom Brain Bank Criteria.

3. PD patients without cognitive or psychiatric disturbances, as measured by the baseline assessment.

4. Prescription of symptomatic therapy with L-Dopa or dopamine agonists based on functional impairment attributed to PD. This will be based on the participant's physician criteria based on:

   • Involvement of the dominant hand and/or upper limbs.
   • Employed patients which the disease impairs their ability to work.

5. Daily computer use > 30 minutes

Exclusion Criteria

1. Mild cognitive impairment or dementia.
2. Psychiatric symptoms
3. Expected or current use of sedative medication (benzodiazepines, opiates, antihistaminergic drugs).
4. Neuroleptic use.
5. History of parkinsonism for the controls.
6. Severe osteo-articular problems with upper limb functional limitation (amputations, severe osteo-arthritis).
7. Alcohol risk use (>40 gr/day or 4 standard drinks for male / >24gr/day or 2 standard drinks for female).
8. Narcolepsy or other sleep disorder producing hypersomnia (obstructive apnea, acute confusional states).
9. Any other life- threatening condition (advanced cancer, severe hepatic or renal insufficiencies.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Percentage of participants with a motor response to medication > 4 UPDRS-III points detected by the developed algorithm (sensitivity to a motor change).	24-weeks	A diagnostic table will be computed with all the study subjects. Those subjects with a clinical relevant response to medication (\> 4 points in UPDRS - III) will be considered as true positives. Then, the accuracy of the typing test to detect them will be evaluated. For this purpose, the sensitivity, specificity, predictive values and ROC curve of a classification algorithm based on our nQ index will be computed. This will allow us assessing the validity of the test to identify a motor change. detected by the developed algorithm (sensitivity to a motor change).

Secondary Outcome Measures

Name	Time	Method
Agreement between nQ and UPDRS motor subscale	4,8,16,24-weeks	Correlation (Spearman Rho) analyses between the indices and UPDRS
Comparison between nQ and the different motor tests (Purdue Pegboard test score & Alternating Finger Tapping)	4,8,16,24-weeks	Correlation (Spearman Rho) between the indices and motor test scores
Comparison between nQ and the CISI-PD, PDQ-39 and NMSS scales	4,8,16,24-weeks	Correlation (Spearman Rho) between the indices and the CISI-PD, PDQ-39 and NMSS scales.
Effect of dopaminergic medication measured by nQ	4,8,16,24-weeks	Correlation (Spearman Rho) between the indices and drug titration measured in L-Dopa equivalent milligrams
Stability of the nQ index in a less controlled environment ("home-setting").	Week 1	Bland-Altman analyses to evaluate the stability of the indices in different days where the medication was not changed and therefore a change should not be expected

Trial Locations

Locations (6)

Hospital de La Princesa; 🇪🇸 Madrid, Spain

Hospital Ramón y Cajal; 🇪🇸 Madrid, Spain

Hospital Universitario HM Puerta del Sur - Centro Integral de Neurociencias A.C.; 🇪🇸 Mostoles, Madrid, Spain

Hospital 12 de Octubre; 🇪🇸 Madrid, Please Select, Spain

Fundacion Hospital Alcorcón; 🇪🇸 Alcorcón, Madrid, Spain

Hospital Clínico San Carlos; 🇪🇸 Madrid, Spain