This is an open label, single arm interventional trial with subretinal injection of rAAV2.REP1 and fellow eye comparison

Choroideremia

rAAV2.REP1

University Hospital Tuebingen, Center for Ophthalmology

THOR - Tübingen Choroideremia Gene Therapy Trial

THOR - Tübingen Choroideremia Gene Therapy Trial Open Label Phase 2 Clinical Trial Using an Adeno-associated Viral Vector (AAV2) Encoding Rab-escort Protein 1 (REP1)

Change from baseline in best corrected visual acuity in treated eye, compared to untreated control eye up to 24 months after vector administration

improved retinal anatomy in treated eye compared to the untreated control eye 24 months after vector administration

improved visual function in treated eye compared to the untreated control eye 24 months after vector administration

improved visual function other than best corrected visual acuity in treated eye compared to the untreated control eye 24 months after vector administration (scale)

improved visual function other than best corrected visual acuity in treated eye compared to the untreated control eye 24 months after vector administration (physiological parameter)

STZ eyetrial

University Hospital Tuebingen

flecainide x 6 months, then crossover to sotalol x 6 months

sotalol x 6 months, then crossover to flecainide x 6 months

Atrial Fibrillation

flecainide up to 150mg twice daily for the control of atrial fibrillation

Flecainide

sotalol up to 120mg twice daily for the control of atrial fibrillation

Sotalol

Jesse Brown VA Medical Center

Rush University Medical Center

University of Illinois at Chicago

Advocate Christ Medical Center

Pharmacogenetic Study of Antiarrhythmic Drugs for Atrial Fibrillation

A Prospective, Multi-Center, Randomized, Open Label Trial to Determine if a Common Atrial Fibrillation Risk Locus Modulates Differential Response to Antiarrhythmic Drugs

Subjects will be monitored with the Medtronic Reveal LINQ Insertable Cardiac Monitor (ICM) system to assess AF burden. The device will be programmed to optimize the memory for storing AF episode..

Quality of life assessment: Patients will be asked to fill out the AFEQT quality of life questionnaire baseline (study randomization), two, four, six, eight, ten, and 12 months (completion of the study). The questionnaire at the end of the 6rd month will be administered just prior to stopping the first study drug. The validated questionnaire is comprised of 20 questions about AF symptoms with answers given on a Likert scale. The questionnaire will be provided to the patients in paper format either in person or by mail, as applicable. A follow-up phone call will be made to each patient to ensure that the questionnaire is completed and returned.

Dawood Darbar, MD

Professor of Medicine

Medtronic

2 hours daily patching of the sound eye plus one hour near activities while patching

Bangerter filter worn on sound eye spectacles lens full time plus at least one hour near activities

Patching

Bangerter Filters

Total

Age, Customized

Sex: Female, Male

Race/Ethnicity, Customized

Region of Enrollment

Prior treatment for amblyopia at enrollment

Cause of amblyopia

Visual acuity was measured in each eye using the Amblyopia Treatment Study (ATS) visual acuity testing protocol resulting in a Snellen acuity score that can range from 20/16 to 20/800 for ages 3 to <7; or with the electronic early treatment diabetic retinopathy study (E-ETDRS) method for 7 to <10 year olds which resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 being the best. Scores were converted to log of minimum angle of resolution (logMAR) equivalents for analyses (lower logMAR value is better than higher logMAR).

Distance visual acuity in amblyopic eye

Mean (SD) Distance Visual Acuity in Amblyopic Eye

Visual acuity was measured with the Amblyopia Treatment Study single-surround HOTV (ATS-HOTV) method for subjects aged 3 to <7 years or the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) method for subjects aged 7 to <10 years.

Distance visual acuity in fellow eye

Mean (SD) Distance Visual Acuity in Fellow Eye

The difference between eyes in logMAR acuity was calculated with positive values indicating sound eye better. One letter = .02 logMAR, .1 logMAR = 5 letters or one line of visual acuity.

Intereye acuity difference

Spherical equivalent in diopters defined from cycloplegic refraction as sphere plus half the cylinder value

Spherical equivalent in amblyopic eye

Spherical equivalent in diopters defined from cycloplegic refraction as sphere plus half the cylinder value.

Mean (SD) spherical equivalent in amblyopic eye

Spherical equivalent in fellow eye

Mean (SD) spherical equivalent in fellow eye

Bangerter

Distribution of Visual Acuity in the Amblyopic Eye at 24 Weeks

Mean (SD) of Amblyopic Eye Visual Acuity at 24 Weeks

Visual acuity was measured in each eye using the Amblyopia Treatment Study (ATS) testing protocol resulting in a Snellen acuity score for 3 to <7 year olds; or with the electronic early treatment diabetic retinopathy study (E-ETDRS) method for 7 to <10 year olds, resulting in a letter score that could range from 0 to 97 letters (0 worst; 97 best). Scores were converted to log of minimum angle of resolution (logMAR)(lower logMAR indicates better score). 'Worse' indicates acuity at 24 weeks is worse than acuity at baseline; 'Better' indicates acuity at 24 weeks is better than acuity at baseline.

Distribution of Change in Amblyopic Eye Visual Acuity Scores From Baseline to 24 Weeks

Visual acuity was measured in each eye using the Amblyopia Treatment Study (ATS) testing protocol resulting in a Snellen acuity score for 3 to <7 year olds; or with the electronic early treatment diabetic retinopathy study (E-ETDRS) method for 7 to <10 year olds, resulting in a letter score that could range from 0 to 97 letters (0 worst; 97 best). Scores were converted to log of minimum angle of resolution (logMAR)(lower logMAR indicates better score). Change from baseline to 24 weeks was calculated. A positive difference indicates improvement (one logMAR line = 5 letters or one Snellen line).

Mean Change in Amblyopic Eye Visual Acuity From Baseline to 24 Weeks

Visual acuity was measured in each eye using the Amblyopia Treatment Study (ATS) testing protocol resulting in a Snellen acuity score for 3 to <7 year olds; or with the electronic early treatment diabetic retinopathy study (E-ETDRS) method for 7 to <10 year olds, resulting in a letter score that could range from 0 to 97 letters (0 worst; 97 best). Scores were converted to log of minimum angle of resolution (logMAR)(lower logMAR indicates better score). A positive interocular difference indicates worse acuity in the amblyopic eye (one logMAR line = 5 letters or one Snellen line).

Mean Interocular Difference at 24 Weeks

Distribution of Subjects With Interocular Difference <1 logMAR Line at 24 Weeks

Distribution of Subjects With >= 20/25 Amblyopic Eye Visual Acuity at 24 Weeks

Distribution of Subjects With 3 or More Lines of Improvement

The distribution of the number of participants in each patient characteristic category at the 24-week outcome examination was found (for example, the number of participants at 24 weeks who were 3 to <5 years old at the time of enrollment).

Distribution of Patient Characteristics at the 24-week Outcome Exam.

Mean and SD of Change in Visual Acuity in the Amblyopic Eye From Baseline to 24-Week Outcome Examination According to Patient Characteristics

The Randot Preschool Stereotest measures stereopsis from 800 to 40 seconds of arc. It is designed as a matching game in which the patient matches pictures in a test booklet wearing special glasses. A subject can fail the pretest (not see any pictures) or can score >800 (the worst), 800, 400, 200, 100, 60, or 40 (the best). If two shapes are identified correctly the patient moves to the next lower level. A failed test occurs when the patient cannot identify any shapes. A change of 1 level is a movement of 1 step in the scale (decrease shows improvement - ex. 100 to 60 is 1 level improved).

Distribution of Change in Randot Preschool Stereoacuity From Baseline to 24-Week Outcome by Treatment Group: All Subjects

Distribution of Change in Randot Preschool Stereoacuity From Baseline to 24-week Outcome by Treatment Group: Subjects With Anisometropia and No Strabismus

Distribution of Change in Fellow Eye Visual Acuity From Baseline to 24 Weeks

Mean Change in Fellow Eye Visual Acuity From Baseline to 24 Weeks

The Parental Amblyopia Treatment Index consists of 18 likert-type questions evaluating the impact of treatment on the patient and family. Questions are answered on a scale from 'Strongly Disagree' to 'Strongly Agree.' For analysis, values were coded numerically with integers from 5 (strongly agree) to 1 (strongly disagree) (0 was assigned to 'non-applicable' answers). The scores were summed and averaged for each individual (total sums could range from 0 to 90; means could range from 0 to 5). A mean across all individuals was computed from the individual means.

Impact of Treatment on Patient and Family at 6 Weeks

Impact of Treatment on Patient and Family at 24 Weeks

The Parental Amblyopia Treatment Index consists of 18 likert-type questions evaluating the impact of treatment on the patient and family (8 of these questions pertain to adverse effects of treatment). Questions are answered on a scale from 'Strongly Disagree' to 'Strongly Agree.' For analysis, values were coded numerically with integers from 5 (strongly agree) to 1 (strongly disagree) (0 was assigned to 'non-applicable' answers). The scores for these 8 questions were summed and averaged for each individual (total sums could range from 0 to 40). A mean across all individuals was computed.

Adverse Effects of Treatment on Patient and Family at 6 Weeks

Adverse Effects of Treatment on Patient and Family at 24 Weeks

The Parental Amblyopia Treatment Index consists of 18 likert-type questions evaluating the impact of treatment on the patient and family (7 of these questions pertain to compliance of treatment). Questions are answered on a scale from 'Strongly Disagree' to 'Strongly Agree.' For analysis, values were coded numerically with integers from 5 (strongly agree) to 1 (strongly disagree) (0 was assigned to 'non-applicable' answers). The scores for these 7 questions were summed and averaged for each individual (total sums could range from 0 to 35). A mean across all individuals was computed.

Compliance With Treatment at 6 Weeks

Compliance With Treatment at 24 Weeks

The Parental Amblyopia Treatment Index consists of 18 likert-type questions evaluating the impact of treatment on the patient and family (2 of these questions pertain to social stigma of treatment). Questions are answered on a scale from 'Strongly Disagree' to 'Strongly Agree.' For analysis, values were coded numerically with integers from 5 (strongly agree) to 1 (strongly disagree) (0 was assigned to 'non-applicable' answers). The scores for these 2 questions were summed and averaged for each individual (total sums could range from 0 to 10). A mean across all individuals was computed.

Social Stigma From Treatment at 6 Weeks

Social Stigma From Treatment at 24 Weeks

Overall Study

Raymond Kraker, MSPH

Amblyopia

Bangerter filter worn on sound eye spectacle lens full time

amblyopia/fiebre

THOR - Tübingen Choroideremia Gene Therapy Trial

Pharmacogenetic Study of Antiarrhythmic Drugs for Atrial Fibrillation

Full-time Bangerter Filters Versus Part-time Daily Patching for Moderate Amblyopia in Children

Plasma and Abscess Fluid Pharmacokinetics of Cefpirome and Moxifloxacin After Single and Multiple Dose Administration

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