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

Motor Response to Dopaminergic Therapy in a Population of de Novo Parkinson's Disease Cases Quantified Via Typing Analyses - -neuroQWERTY

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.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease

• Study Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28034
    • Hospital Ramón y Cajal
  • Madrid, Spain, 28006
    • Hospital De La Princesa
  • Madrid
    • Alcorcón, Madrid, Spain, 28922
      • Fundación Hospital Alcorcón
    • Mostoles, Madrid, Spain, 28938
      • Hospital Universitario HM Puerta del Sur - Centro Integral de Neurociencias A.C.
  • Please Select
    • Madrid, Please Select, Spain, 28041
      • Hospital 12 de Octubre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

A group of early Parkinson's disease participants who are going to be prescribed dopaminergic agents and a group of healthy volunteers will be recruited at the different collaborating institutions.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Healthy controls; A sample of 30 healthy volunteers will be recruited to compare the typing signal with that of the cases.
Early Parkinson's disease cases; A sample of 30 early PD cases (i.e. less than five years of disease and no axial signs or fluctuations) that are going to be prescribed de novo dopaminergic therapy will be recruited.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with a motor response to medication > 4 UPDRS-III points detected by the developed algorithm (sensitivity to a motor change).	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).	24-weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Agreement between nQ and UPDRS motor subscale	Correlation (Spearman Rho) analyses between the indices and UPDRS	4,8,16,24-weeks
Comparison between nQ and the different motor tests (Purdue Pegboard test score & Alternating Finger Tapping)	Correlation (Spearman Rho) between the indices and motor test scores	4,8,16,24-weeks
Effect of dopaminergic medication measured by nQ	Correlation (Spearman Rho) between the indices and drug titration measured in L-Dopa equivalent milligrams	4,8,16,24-weeks
Comparison between nQ and the CISI-PD, PDQ-39 and NMSS scales	Correlation (Spearman Rho) between the indices and the CISI-PD, PDQ-39 and NMSS scales.	4,8,16,24-weeks
Stability of the nQ index in a less controlled environment ("home-setting").	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	Week 1

Collaborators and Investigators

• Sponsor: Fundación de investigación HM
• Collaborators: Massachusetts Institute of Technology; Hospital Universitario Ramon y Cajal; Michael J. Fox Foundation for Parkinson's Research; Hospital Universitario 12 de Octubre; Hospital San Carlos, Madrid; Fundación de Investigación Biomédica - Hospital Universitario de La Princesa; Hospital Universitario Fundación Alcorcón
• Investigators: Principal Investigator: Jose Obeso, MD, PhD, Director at Centro Integral de Neurociencias A.C.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2015
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: August 6, 2015
• First Submitted That Met QC Criteria: August 10, 2015
• First Posted (Estimate): August 13, 2015

Study Record Updates

• Last Update Posted (Actual): April 4, 2019
• Last Update Submitted That Met QC Criteria: April 2, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Patient Outcome Assessment; Hypokinesia
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: 15.05.796-GHM