A First Study in Healthy Volunteers of a New Mobile Phone Application Measuring the Eyes Before and After Medication

A First-in-human Explorative Pilot Study in Healthy Volunteers Measuring Eye Parameters With a New Mobile Phone Application for Future Monitoring of Patients in Treatment of Substance Use Disorder

This is a pre-market, explorative, early feasibility, pilot, controlled clinical investigation designed to collect initial clinical data on the medical device Previct Drugs.

Study Overview

• Status: Completed
• Conditions: Drug Abuse
• Intervention / Treatment: Device: Previct Drugs

Detailed Description

This first study will give valuable information on the feasibility of Previct Drugs function to measure pupils and eye movements and to evaluate if there are any changes in the pupillometric parameters before and after intake of a medicinal product. It will also provide information on the usability of the device. Drug intake will in this first investigation be simulated by a controlled single application of commonly therapeutically used medicinal products from the following classes of drugs: phenethylamines (D1), benzodiazepines (D2), cannabinoids (D3), and opioids (D4).

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Leiden, Netherlands, 2333 ZA
    • Leiden University Medical Center (LUMC) Department of Anesthesiology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male or female healthy volunteers
• Age 18 to 70 years
• BMI between 18.5-30 kg/m2
• Weight between 50-100 kg
• Healthy as determined by the investigator or designee based on pre-study medical and surgical history and a health examination at enrollment
• Women of childbearing potential (defined as all women who are not surgically sterile or postmenopausal for at least 1 year prior to enrollment) must have a negative urine pregnancy test at enrollment and at visit 2 and must agree to use a medically acceptable contraception from enrollment until study completion
• No current drug usage defined as a negative urine drug test at enrollment and at visit 2
• Able to use Previct Drugs after initial training (defined as successfully performing a test after trying maximum three times per measurement)
• Been informed of the nature, the scope, and the relevance of the clinical investigation
• Voluntarily agreed on participation and has duly singed the Informed Consent Form

Exclusion Criteria:

• Participating in another clinical investigation which may affect the study outcome according to clinical judgement
• Pregnancy or Lactating
• Blind
• Deaf
• Abnormal ECG (QTc time >450 ms) at enrollment
• Current or recent history of alcohol misuse assessed by AUDIT where ≥6 points for women or ≥8 points for men indicates a potential misuse
• Current or history of psychiatric disorder or drug misuse assessed by M.I.N.I where the outcome will be based on clinical judgement
• Any disease or condition that may influence pupillary reflexes based on clinical judgement
• Undergone eye surgery that may influence pupillary reflexes based on clinical judgement
• Ongoing treatment with medications which may interfere with eye measurements based on clinical judgement
• Ongoing treatment with medications which may interfere with any of the medicinal products to be used
• History or presence of allergy or serious reaction to the medicinal products to be used
• History or presence of cardiovascular disease, e.g., arteriosclerosis, hypertension, or cor pulmonale
• History or presence of sleep-related breath disorder
• History or presence of gastrointestinal disease, e.g., paralytic ileus, acute abdomen, delayed gastric emptying, or chronic constipation
• History or presence of pulmonary disease, e.g., acute pulmonary insufficiency, severe respiratory depression with hypoxia, chronic obstructive lung disease, or bronchial asthma
• History or presence of autoimmune neuromuscular disease, e.g., myasthenia gravis
• Not able to read or understand the local language
• Any other condition that as judged by the investigator may make the follow-up or investigation inappropriate
• That according to the Declaration of Helsinki is deemed unsuitable for study enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single application of phenethylamines (D1); Evaluation of Previct Drugs' function to measure pupils and eye movements and to evaluate if there are any changes in the pupillometric parameters before and after intake of phenethylamines.	Device: Previct Drugs; Previct Drugs is a new non CE-marked eHealth system intended to be used for future monitoring and treatment of patients with substance use disorder (SUD). Previct Drugs consists of an application (app) to be installed on a smartphone, a web-based careportal to be accessed from a computer by the healthcare professional for administration and access of registered data, and a database for storage, handling, and analysis of reported data. Previct Drugs is intended to be used by healthcare professionals and patients within treatment of SUD.
Experimental: Single application of benzodiazepines (D2); Evaluation of Previct Drugs' function to measure pupils and eye movements and to evaluate if there are any changes in the pupillometric parameters before and after intake of benzodiazepines.	Device: Previct Drugs; Previct Drugs is a new non CE-marked eHealth system intended to be used for future monitoring and treatment of patients with substance use disorder (SUD). Previct Drugs consists of an application (app) to be installed on a smartphone, a web-based careportal to be accessed from a computer by the healthcare professional for administration and access of registered data, and a database for storage, handling, and analysis of reported data. Previct Drugs is intended to be used by healthcare professionals and patients within treatment of SUD.
Experimental: Single application of cannabinoids (D3); Evaluation of Previct Drugs' function to measure pupils and eye movements and to evaluate if there are any changes in the pupillometric parameters before and after intake of cannabinoids.	Device: Previct Drugs; Previct Drugs is a new non CE-marked eHealth system intended to be used for future monitoring and treatment of patients with substance use disorder (SUD). Previct Drugs consists of an application (app) to be installed on a smartphone, a web-based careportal to be accessed from a computer by the healthcare professional for administration and access of registered data, and a database for storage, handling, and analysis of reported data. Previct Drugs is intended to be used by healthcare professionals and patients within treatment of SUD.
Experimental: Single application of opioids (D4); Evaluation of Previct Drugs' function to measure pupils and eye movements and to evaluate if there are any changes in the pupillometric parameters before and after intake of opioids.	Device: Previct Drugs; Previct Drugs is a new non CE-marked eHealth system intended to be used for future monitoring and treatment of patients with substance use disorder (SUD). Previct Drugs consists of an application (app) to be installed on a smartphone, a web-based careportal to be accessed from a computer by the healthcare professional for administration and access of registered data, and a database for storage, handling, and analysis of reported data. Previct Drugs is intended to be used by healthcare professionals and patients within treatment of SUD.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Use of Self-administered Pupillometry Using a Mobile Phone Application Can be Used to Collect Pupillograms Before and Under the Influence of Phenethylamines, Benzodiazepines, Cannabinoids, and Opioids (D1-D4).	For each medicinal product (D1-D4), the fraction of collected pupillometry data from the mobile phone application at baseline and under the influence of D1-D4, which can be transformed into pre-defined key features using native pupillogram. A key feature represents an eye characteristic (such as pupil size, iris position, and the similar). A successful transformation is characterised by underlying quality control algorithms approving the extracted magnitude, where poor quality pupillograms are rejected from analysis. Each attempt to transform a pupillogram into key features is denoted an "Attempt", and the successful transformation is denoted a "Successful attempt".	Day 7 +/- 2 days (Visit 2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Use of Self-administered Pupillometry Using a Mobile Phone Application, After Refining the Method for Establishing Pupillograms, Can be Used to Collect Pupillograms Before and Under the Influence of Each Medicinal Product (D1-D4).	For each medicinal product (D1-D4), the fraction of collected pupillometry data from the mobile phone application at baseline and under the influence of D1-D4, which can be transformed into pre-defined key features using refined pupillogram. A key feature represents an eye characteristic (such as pupil size, iris position, and the similar). A successful transformation is characterised by underlying quality control algorithms approving the extracted magnitude, where poor quality pupillograms are rejected from analysis. Each attempt to transform a pupillogram into key features is denoted an "Attempt", and the successful transformation is denoted a "Successful attempt.	Day 7 +/- 2 days (Visit 2)
Number of Key Features With Change From Baseline to Peak Concentration in Plasma, Using Refined Pupillograms.	For each medicinal product (D1-D4), number of changed key features from baseline to the LC-MS/MS (Liquid Chromatography Tandem Mass-Spectroscopy) verified peak concentration in plasma after administration of medicinal product at visit 2 using refined pupillograms. Each of the 24 key features represents an eye characteristic (such as pupil size, iris position, and the similar). A key feature is considered "changed" if the difference between averages at baseline and peak concentration is significant (p<0.05). Key features were available from two conditions, one condition where pupillograms and corresponding key features were collected in dim ambient light (50 Lux) and one condition where pupillograms and corresponding key features were collected in bright ambient light (500 Lux). The Outcome Measure is reported for both ambient light conditions.	Day 7 +/- 2 days (Visit 2)
Number of Key Features for Which Correlation Between Pupillometric Variables and Concentration in Plasma Over Time is Significant for Each Medicinal Product D1-D4 and Ambient Light Condition.	For each medicinal product (D1-D4), number of significant correlations between key features and plasma concentration over time using refined pupillograms. A key feature represents an eye characteristic (such as pupil size, iris position, and the similar). A key feature is considered "correlated" if the slope in a linear regression is significantly different from zero (p<0.05). The term correlated over time refers to data collected during 5 hours at Visit 2 after administration of D1-D4. Key features were available from two conditions, one condition where pupillograms and corresponding key features were collected in dim ambient light (50 Lux) and one condition where pupillograms and corresponding key features were collected in bright ambient light (500 Lux). The Outcome Measure is reported for both ambient light conditions.	Day 7 +/- 2 days (Visit 2)
Number of Key Features With Change From Baseline to 5 Hours After Administration of Medicinal Product, Using Refined Pupillograms.	For each medicinal product (D1-D4), number of changed key features from baseline to 5 hours after administration of medicinal product at visit 2 using refined pupillograms. A key feature represents an eye characteristic (such as pupil size, iris position, and the similar). A key feature is considered "changed" if the difference between averages at baseline and at 5 hours is significant (p<0.05). Key features were available from two conditions, one condition where pupillograms and corresponding key features were collected in dim ambient light (50 Lux) and one condition where pupillograms and corresponding key features were collected in bright ambient light (500 Lux). The Outcome Measure is reported for both ambient light conditions.	Day 7 +/- 2 days (Visit 2)
Number of Correct Classifications of Subjects, Evaluated Using a Combination of Different Pupillometric Variables for Indicating Use of Each Medicinal Product D1-D4 and Ambient Light Condition.	For each medicinal product (D1-D4), evaluate known combinations of key features that changes from baseline to the LC-MS/MS verified peak concentration in plasma after administration of medicinal product at visit 2 using refined pupillograms. A key feature represents an eye characteristic (such as pupil size, iris position, and the similar). A combination of key features collected at peak plasma concentration was used to build a logistic regression classifier, and the resulting counts of true positives, true negatives, false positives, and false negatives are presented. Key features were available from two conditions, one condition where pupillograms and corresponding key features were collected in dim ambient light (50 Lux) and one condition where pupillograms and corresponding key features were collected in bright ambient light (500 Lux). The Outcome Measure is reported for both ambient light conditions. Key feature values were missing in a few instances, as shown in the table.	Day 7 +/- 2 days (Visit 2)
Usability Questionnaire - Question 1	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 1. How would you grade the instructions for use? Response options: Not understandable; Could only understand some parts; Could understand most parts; Could understand almost every part; Fully understandable	Day 7 +/- 2 days (Visit 2)
Usability Questionnaire - Question 2	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 2. Was Previct Drugs easy to use correctly based on the information in the Instructions For Use (IFU)? Response options: Yes; No	Day 7 +/- 2 days (Visit 2)
Usability Questionnaire - Question 4	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 4. How did you experience the verbal instructions during a test with Previct Drugs? Response options: Very easy to understand; Easy to understand; Nor easy or difficult to understand; Difficult to understand; Very difficult to understand	Day 7 +/- 2 days (Visit 2)
Usability Questionnaire - Question 5	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 5. Before starting a test, the App prompted you with a few written instructions. Did you read the instructions? Response options: Yes; No	Day 7 +/- 2 days (Visit 2)
Usability Questionnaire - Question 7	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 7. How did you experience performing a test with Previct Drugs (from opening of the App until the test was completed)? Response options: Very easy to perform; Easy to perform; Nor easy or difficult to perform; Difficult to perform; Very difficult to perform	Day 7 +/- 2 days (Visit 2)
Usability Questionnaire - Question 8	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 8. During a test with Previct Drugs, did you at any time have to tilt the mobile against something to be able to perform a measurement? Response options: Yes; No	Day 7 +/- 2 days (Visit 2)
Usability Questionnaire - Question 9	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 9. If Yes (to question 8), how often did you have to tilt the mobile against something: Response options: One occasion; Several occasions; Most occasions; All occasions	Day 7 +/- 2 days (Visit 2)
Usability Questionnaire - Question 10	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 10. According to you, how many minutes did a test with Previct Drugs take in general? From start to end. Response options: < 5 minutes; 5-7 minutes; > 7 minutes	Day 7 +/- 2 days (Visit 2)
Usability Questionnaire - Question 11	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 11. Did you receive a notification when it was time for a test with Previct Drugs? Response options: Yes; Most of the times; I did not receive any notifications	Day 7 +/- 2 days (Visit 2)
Usability Questionnaire - Question 12	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 12. Did you notice any issues during usage of Previct Drugs? Response options: No; Yes	Day 7 +/- 2 days (Visit 2)
Usability Questionnaire - Question 13	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 13. Did you require any assistance from the study personnel (e.g., through phone) during the usage of Previct Drugs? Response options: Yes; No	Day 7 +/- 2 days (Visit 2)
Usability Questionnaire - Question 15	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 15. If Yes (to question 13), how often did you require assistance? Response options: One occasion; Several occasions; Most occasions; All occasions	Day 7 +/- 2 days (Visit 2)
Usability Questionnaire - Question 16	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 16. When starting a measurement, how was your experience finding the right conditions to start the measurement? Response options: Very easy; Easy; Nor easy or difficult; Difficult; Very difficult	Day 7 +/- 2 days (Visit 2)
Usability Questionnaire - Question 18	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 18. How did you experience performing a Nystagmus (look to your extreme right and left) test? Response options: Very easy to perform; Easy to perform; Nor easy or difficult to perform; Difficult to perform; Very difficult to perform	Day 7 +/- 2 days (Visit 2)
Usability Questionnaire - Question 20	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 20. According to you, how many minutes did a Nystagmus test take (from starting test until analyzed)? Response options: < 1 minute; 1-2 minutes; > 3 minutes	Day 7 +/- 2 days (Visit 2)
Usability Questionnaire - Question 21	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 21. How often did you have to redo a Nystagmus test? Response options: No occasion; One occasion; Several occasions; Most occasions; All occasions	Day 7 +/- 2 days (Visit 2)
Usability Questionnaire - Question 23	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 23. In general, how easy is it for you to cross your eyes? Response options: Very easy; Easy; Nor easy or difficult; Difficult; Very difficult	Day 7 +/- 2 days (Visit 2)
Usability Questionnaire - Question 24	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 24. How did you experience performing a Cross Eyes test? Response options: Very easy to perform; Easy to perform; Nor easy or difficult to perform; Difficult to perform; Very difficult to perform	Day 7 +/- 2 days (Visit 2)
Usability Questionnaire - Question 26	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 26. According to you, how many minutes did a Cross Eyes test take (from starting until analyzed)? Response options: < 1 minute; 1-2 minutes; > 3 minutes	Day 7 +/- 2 days (Visit 2)
Usability Questionnaire - Question 27	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 27. How often did you have to redo a Cross Eyes test? Response options: No occasion; One occasion; Several occasions; Most occasions; All occasions	Day 7 +/- 2 days (Visit 2)
Usability Questionnaire - Question 29	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 29. How did you experience performing a Contraction test? Response options: Very easy to perform; Easy to perform; Nor easy or difficult to perform; Difficult to perform; Very difficult to perform	Day 7 +/- 2 days (Visit 2)
Usability Questionnaire - Question 31	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 31. How was your experience turning your mobile when asked to? Response options: Very easy to perform; Easy to perform; Nor easy or difficult to perform; Difficult to perform; Very difficult to perform	Day 7 +/- 2 days (Visit 2)
Usability Questionnaire - Question 33	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 33. According to you, how many minutes did a Contraction test take (from starting test until analyzed)? Response options: < 1 minute; 1-2 minutes; > 3 minutes	Day 7 +/- 2 days (Visit 2)
Usability Questionnaire - Question 34	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 34. How often did you have to redo a Contraction test? Response options: No occasion; One occasion; Several occasions; Most occasions; All occasions	Day 7 +/- 2 days (Visit 2)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate safety of using the mobile phone application Previct Drugs	The incidence and severity of adverse events associated with Previct Drugs	Through study completion, an average of 10 days

Collaborators and Investigators

• Sponsor: Kontigo Care AB
• Investigators: Study Chair: Markku Hämäläinen, PhD, Kontigo Care AB

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2023
• Primary Completion (Actual): July 19, 2023
• Study Completion (Actual): July 19, 2023

Study Registration Dates

• First Submitted: January 30, 2023
• First Submitted That Met QC Criteria: February 8, 2023
• First Posted (Actual): February 16, 2023

Study Record Updates

• Last Update Posted (Actual): April 2, 2025
• Last Update Submitted That Met QC Criteria: April 1, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders
• Other Study ID Numbers: KCClin01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No