Trial Outcomes & Findings for Convergence Insufficiency Treatment Study (CITS) (NCT NCT01515943)

Results Overview

Pairwise treatment group comparison (HB-C versus HB-PU) of the percentages of participants meeting success criteria using binomial regression adjusting for baseline covariates of CISS score (\<28 points vs ≥ 28 points), mean NPC break (\<10 cm vs ≥ 10 cm), and mean PFV blur (≥ 15 PD vs \<15 PD) using linear contrasts with Bonferroni adjustment for multiple comparisons (Type I error rate = 2.5%). Overall success was defined as meeting all of the following criteria at 12 weeks: 1. Convergence Insufficiency Symptom Survey (CISS): 12-week score \<16 points and at least 9-point improvement from baseline at 12 weeks 2. Near point of convergence (NPC) break: 12-week/baseline mean NPC break \<0.763 and a mean 12-week NPC break \<6 cm 3. Positive fusional vergence (PFV) blur: 12-week/baseline mean PFV blur \>1.419 and a mean 12-week PFV break \>15 pd

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

204 participants

Primary outcome timeframe

12 weeks after randomization (baseline)

Results posted on

2017-04-12

Participant Flow

Participant milestones

Participant milestones
Measure	Computer-based Therapy (CBT) The CBT group will be assigned active home-based computer vergence/accommodative therapy (15 minutes/day) plus placebo yoked prism flipper therapy (5 minutes/day) for a total of 20/minutes per day, 5 days per week for the 12-week treatment phase. Active home-based computer vergence/accommodative therapy: At enrollment, subjects will be prescribed 15 minutes/day of active home-based computer therapy for 5 days/week during the 12 week treatment phase. Active home-based computer therapy will be provided the Home Therapy System (HTS) computer software and will include both fusional vergence and accommodative therapy. Subjects will perform the computer therapy while wearing red/blue glasses and accommodative therapy will be performed using the HTS accommodative flippers. Please refer to the procedures manual for further details. Placebo yoked prism flippers: Subjects will be prescribed 5 minutes/day of placebo yoked prism flipper therapy for 5 days/week during the 12 week treatment	Near Target Push-up (NTP) The NTP group will be assigned placebo home-based computer vergence/accommodative therapy (5 minutes/day) plus near target push-ups (15 minutes/day) for a total of 20/minutes per day, 5 days per week for the 12-week treatment phase. Near target push-ups: At enrollment, subjects will be prescribed 15 minutes/day (3 sessions of 5 minutes each) of near target push-ups (NTP) for 5 days/week during the 12-week treatment phase. An alphabet pencil will be used as the target and an index card placed in the background will provide physiological diplopia control. With the pencil positioned at arm's length directly between the subject's eyes, the subject will slowly bring the pencil toward his/her nose while focusing on the small letter on the pencil. When the subject is no longer able to maintain a single image of the pencil, he/she will slowly move the target away from the nose until the pencil becomes single again. This procedure will be repeated several times.	Placebo The placebo group will be assigned placebo home-based computer vergence/accommodative therapy (15 minutes/day) plus placebo yoked prism flipper therapy (5 minutes/day) for a total of 20/minutes per day, 5 days per week for the 12-week treatment phase. Placebo home-based computer vergence/accommodative therapy: At enrollment, subjects will be prescribed either 5 minutes/day (NTP group) or 15 minutes/day (Placebo group) of placebo home-based computer therapy for 5 days/week during the 12 week treatment phase. Placebo computer-based therapy will be provided by the Home Therapy System (HTS) computer software. The vergence procedures are similar to the active version, however, the tasks will be modified to ensure no demand on the vergence system and no accommodative therapy is included in the placebo version. Please refer to the procedures manual for further details. Placebo yoked prism flippers: Subjects will be prescribed 5 minutes/day of placebo yoked prism flipper therapy for 5
Overall Study STARTED	75	85	44
Overall Study COMPLETED	69	69	31
Overall Study NOT COMPLETED	6	16	13

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Convergence Insufficiency Treatment Study (CITS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Computer-based Therapy (CBT) n=75 Participants The CBT group will be assigned active home-based computer vergence/accommodative therapy (15 minutes/day) plus placebo yoked prism flipper therapy (5 minutes/day) for a total of 20/minutes per day, 5 days per week for the 12-week treatment phase. Active home-based computer vergence/accommodative therapy: At enrollment, subjects will be prescribed 15 minutes/day of active home-based computer therapy for 5 days/week during the 12 week treatment phase. Active home-based computer therapy will be provided the Home Therapy System (HTS) computer software and will include both fusional vergence and accommodative therapy. Subjects will perform the computer therapy while wearing red/blue glasses and accommodative therapy will be performed using the HTS accommodative flippers. Please refer to the procedures manual for further details. Placebo yoked prism flippers: Subjects will be prescribed 5 minutes/day of placebo yoked prism flipper therapy for 5 days/week during the 12 week treatment	Near Target Push-up (NTP) n=85 Participants The NTP group will be assigned placebo home-based computer vergence/accommodative therapy (5 minutes/day) plus near target push-ups (15 minutes/day) for a total of 20/minutes per day, 5 days per week for the 12-week treatment phase. Near target push-ups: At enrollment, subjects will be prescribed 15 minutes/day (3 sessions of 5 minutes each) of near target push-ups (NTP) for 5 days/week during the 12-week treatment phase. An alphabet pencil will be used as the target and an index card placed in the background will provide physiological diplopia control. With the pencil positioned at arm's length directly between the subject's eyes, the subject will slowly bring the pencil toward his/her nose while focusing on the small letter on the pencil. When the subject is no longer able to maintain a single image of the pencil, he/she will slowly move the target away from the nose until the pencil becomes single again. This procedure will be repeated several times. Please refer to the pr	Placebo n=44 Participants The placebo group will be assigned placebo home-based computer vergence/accommodative therapy (15 minutes/day) plus placebo yoked prism flipper therapy (5 minutes/day) for a total of 20/minutes per day, 5 days per week for the 12-week treatment phase. Placebo home-based computer vergence/accommodative therapy: At enrollment, subjects will be prescribed either 5 minutes/day (NTP group) or 15 minutes/day (Placebo group) of placebo home-based computer therapy for 5 days/week during the 12 week treatment phase. Placebo computer-based therapy will be provided by the Home Therapy System (HTS) computer software. The vergence procedures are similar to the active version, however, the tasks will be modified to ensure no demand on the vergence system and no accommodative therapy is included in the placebo version. Please refer to the procedures manual for further details. Placebo yoked prism flippers: Subjects will be prescribed 5 minutes/day of placebo yoked prism flipper therapy for 5	Total n=204 Participants Total of all reporting groups
Age, Categorical <=18 years	75 Participants n=5 Participants	85 Participants n=7 Participants	44 Participants n=5 Participants	204 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	12.2 years STANDARD_DEVIATION 2.4 • n=5 Participants	12.6 years STANDARD_DEVIATION 2.5 • n=7 Participants	12.3 years STANDARD_DEVIATION 2.3 • n=5 Participants	12.4 years STANDARD_DEVIATION 2.4 • n=4 Participants
Sex: Female, Male Female	46 Participants n=5 Participants	46 Participants n=7 Participants	26 Participants n=5 Participants	118 Participants n=4 Participants
Sex: Female, Male Male	29 Participants n=5 Participants	39 Participants n=7 Participants	18 Participants n=5 Participants	86 Participants n=4 Participants
Region of Enrollment United States	75 participants n=5 Participants	85 participants n=7 Participants	44 participants n=5 Participants	204 participants n=4 Participants

PRIMARY outcome

Timeframe: 12 weeks after randomization (baseline)

Population: The analysis was limited to participants who completed the 12-week visit within the pre-specified analysis window (10 to 18 weeks, inclusive).

Pairwise treatment group comparison (HB-C versus HB-PU) of the percentages of participants meeting success criteria using binomial regression adjusting for baseline covariates of CISS score (\<28 points vs ≥ 28 points), mean NPC break (\<10 cm vs ≥ 10 cm), and mean PFV blur (≥ 15 PD vs \<15 PD) using linear contrasts with Bonferroni adjustment for multiple comparisons (Type I error rate = 2.5%). Overall success was defined as meeting all of the following criteria at 12 weeks: 1. Convergence Insufficiency Symptom Survey (CISS): 12-week score \<16 points and at least 9-point improvement from baseline at 12 weeks 2. Near point of convergence (NPC) break: 12-week/baseline mean NPC break \<0.763 and a mean 12-week NPC break \<6 cm 3. Positive fusional vergence (PFV) blur: 12-week/baseline mean PFV blur \>1.419 and a mean 12-week PFV break \>15 pd

Outcome measures

Outcome measures
Measure	Near Target Push-up (NTP) n=69 Participants Prescribed 15 minutes (in full or split into three 5-minute intervals) of a well-defined near target push-up (NTP) procedure and 5 minutes of placebo computer vergence/accommodative therapy (CVAT), 5 days per week for 12 weeks to be performed at home.	Computer-based Therapy (CBT) n=69 Participants Prescribed 15 minutes of active computer vergence/accommodative therapy (CVAT) and 5 minutes of placebo flipper exercises, 5 days per week for 12 weeks to be performed at home.	Placebo n=31 Participants Prescribed 15 minutes of placebo computer vergence/accommodative therapy (CVAT) and 5 minutes of placebo flipper exercises, 5 days per week for 12 weeks to be performed at home.
Treatment Group Comparison of the Percentage of Participants Classified as an Overall Success at 12 Weeks - HB-C Versus HB-PU	15 Participants	16 Participants	5 Participants

PRIMARY outcome

Timeframe: 12-weeks after randomization (baseline)

Population: The analysis was limited to participants who completed the 12-week visit within the pre-specified analysis window (10 to 18 weeks, inclusive).

Pairwise treatment group comparison (HB-C versus Placebo) of the percentages of participants meeting success criteria using binomial regression adjusting for baseline covariates of CISS score (\<28 points vs ≥ 28 points), mean NPC break (\<10 cm vs ≥ 10 cm), and mean PFV blur (≥ 15 PD vs \<15 PD) using linear contrasts with Bonferroni adjustment for multiple comparisons. Overall success was defined as meeting all of the following criteria at 12 weeks: 1. Convergence Insufficiency Symptom Survey (CISS): 12-week score \<16 points and at least 9-point improvement from baseline at 12 weeks 2. Near point of convergence (NPC) break: 12-week/baseline mean NPC break \<0.763 and a mean 12-week NPC break \<6 cm 3. Positive fusional vergence (PFV) blur: 12-week/baseline mean PFV blur \>1.419 and a mean 12-week PFV break \>15 pd

Outcome measures

Outcome measures
Measure	Near Target Push-up (NTP) n=69 Participants Prescribed 15 minutes (in full or split into three 5-minute intervals) of a well-defined near target push-up (NTP) procedure and 5 minutes of placebo computer vergence/accommodative therapy (CVAT), 5 days per week for 12 weeks to be performed at home.	Computer-based Therapy (CBT) n=69 Participants Prescribed 15 minutes of active computer vergence/accommodative therapy (CVAT) and 5 minutes of placebo flipper exercises, 5 days per week for 12 weeks to be performed at home.	Placebo n=31 Participants Prescribed 15 minutes of placebo computer vergence/accommodative therapy (CVAT) and 5 minutes of placebo flipper exercises, 5 days per week for 12 weeks to be performed at home.
Treatment Group Comparison of the Percentage of Participants Classified as an Overall Success at 12 Weeks - HB-C Versus HB-P	15 Participants	16 Participants	5 Participants

SECONDARY outcome

Timeframe: 12 weeks after randomization (baseline)

Population: The analysis was limited to participants who completed the 12-week visit within the pre-specified analysis window (10 to 18 weeks, inclusive). Descriptive statistics were performed to compute the number and proportion of participants by treatment group.

The number of subjects classified as a success based on signs/symptoms at the 12-week visit. Success is based on the Convergency Insufficiency Symptom Survey (CISS) defined as improvement of 9 or more points from baseline and a 12-week score of \<16 points.

Outcome measures

Outcome measures
Measure	Near Target Push-up (NTP) n=69 Participants Prescribed 15 minutes (in full or split into three 5-minute intervals) of a well-defined near target push-up (NTP) procedure and 5 minutes of placebo computer vergence/accommodative therapy (CVAT), 5 days per week for 12 weeks to be performed at home.	Computer-based Therapy (CBT) n=69 Participants Prescribed 15 minutes of active computer vergence/accommodative therapy (CVAT) and 5 minutes of placebo flipper exercises, 5 days per week for 12 weeks to be performed at home.	Placebo n=31 Participants Prescribed 15 minutes of placebo computer vergence/accommodative therapy (CVAT) and 5 minutes of placebo flipper exercises, 5 days per week for 12 weeks to be performed at home.
Number of Participants Classified as Having Met Success Criteria Based on CI Signs/Symptoms at 12 Weeks by Treatment Group	25 participants	28 participants	11 participants

SECONDARY outcome

Timeframe: 12 weeks after randomization (baseline)

Population: The analysis was limited to participants who completed the 12-week visit within the pre-specified analysis window (10 to 18 weeks, inclusive). Descriptive statistics were performed to compute the number and proportion of participants by treatment group.

The number of subjects who are classified as a success based on the mean NPC break at the 12-week visit. Success is based on the mean NPC (near point of convergence) break is defined as having a mean NPC break of \<6 cm at 12 weeks and a 12-week to baseline ratio of \<0.763 for mean NPC break.

Outcome measures

Outcome measures
Measure	Near Target Push-up (NTP) n=69 Participants Prescribed 15 minutes (in full or split into three 5-minute intervals) of a well-defined near target push-up (NTP) procedure and 5 minutes of placebo computer vergence/accommodative therapy (CVAT), 5 days per week for 12 weeks to be performed at home.	Computer-based Therapy (CBT) n=69 Participants Prescribed 15 minutes of active computer vergence/accommodative therapy (CVAT) and 5 minutes of placebo flipper exercises, 5 days per week for 12 weeks to be performed at home.	Placebo n=31 Participants Prescribed 15 minutes of placebo computer vergence/accommodative therapy (CVAT) and 5 minutes of placebo flipper exercises, 5 days per week for 12 weeks to be performed at home.
Number of Participants Classified as Having Met Success Criteria Based on the Mean NPC Break at 12 Weeks by Treatment Group	33 participants	33 participants	11 participants

SECONDARY outcome

Timeframe: 12 weeks after randomization (baseline)

Population: The analysis was limited to participants who completed the 12-week visit within the pre-specified analysis window (10 to 18 weeks, inclusive). Descriptive statistics were performed to compute the number and proportion of participants by treatment group.

The number of subjects who are classified as a success based on the mean PFV blur at the 12-week visit. Success is based on the mean PFV (positive fusional vergence) blur, defined as having a mean PFV blur of \>15 pd at 12 weeks and a 12-week to baseline ratio of \>1.419 for mean PFV blur.

Outcome measures

Outcome measures
Measure	Near Target Push-up (NTP) n=69 Participants Prescribed 15 minutes (in full or split into three 5-minute intervals) of a well-defined near target push-up (NTP) procedure and 5 minutes of placebo computer vergence/accommodative therapy (CVAT), 5 days per week for 12 weeks to be performed at home.	Computer-based Therapy (CBT) n=69 Participants Prescribed 15 minutes of active computer vergence/accommodative therapy (CVAT) and 5 minutes of placebo flipper exercises, 5 days per week for 12 weeks to be performed at home.	Placebo n=69 Participants Prescribed 15 minutes of placebo computer vergence/accommodative therapy (CVAT) and 5 minutes of placebo flipper exercises, 5 days per week for 12 weeks to be performed at home.
Number of Participants Classified as Having Met Success Criteria Based on the Mean PFV Blur at 12 Weeks by Treatment Group	35 participants	49 participants	16 participants

SECONDARY outcome

Timeframe: 12-weeks after randomization (baseline)

Population: The analysis was limited to participants who completed the 12-week visit within the pre-specified analysis window (10 to 18 weeks, inclusive). Descriptive statistics were performed to compute the number and proportion of participants by treatment group.

The number of subjects classified as a success based on clinical measures of CI (mean NPC break \& mean PFV blur) at the 12-week visit. Clinical success is defined according to whether both criteria (below) are met as follows: 1. Near point of convergence (NPC) break: 12-week/baseline mean NPC break \<0.763 and a 12-week mean NPC break \<6 cm 2. Positive fusional vergence (PFV) blur: 12-week/baseline mean PFV blur \>1.419 and a 12-week mean PFV blur \>15 pd

Outcome measures

Outcome measures
Measure	Near Target Push-up (NTP) n=69 Participants Prescribed 15 minutes (in full or split into three 5-minute intervals) of a well-defined near target push-up (NTP) procedure and 5 minutes of placebo computer vergence/accommodative therapy (CVAT), 5 days per week for 12 weeks to be performed at home.	Computer-based Therapy (CBT) n=69 Participants Prescribed 15 minutes of active computer vergence/accommodative therapy (CVAT) and 5 minutes of placebo flipper exercises, 5 days per week for 12 weeks to be performed at home.	Placebo n=31 Participants Prescribed 15 minutes of placebo computer vergence/accommodative therapy (CVAT) and 5 minutes of placebo flipper exercises, 5 days per week for 12 weeks to be performed at home.
Number of Participants Classified as Having Met Success Criteria for Both Clinical Measures at 12 Weeks by Treatment Group	22 participants	30 participants	9 participants

SECONDARY outcome

Timeframe: 12 weeks after randomization (baseline)

Population: The analysis was limited to participants who completed the 12-week visit within the pre-specified analysis window (10 to 18 weeks, inclusive). Descriptive statistics were performed to compute the number and proportion of participants by treatment group.

Improvement in all 3 outcome measures at 12 weeks will be defined as follows: 1. Convergency Insufficiency Symptom Survey (CISS): Improvement of 9 or more points since baseline 2. Near point of convergence (NPC) break: 12-week/baseline mean NPC break \<0.763 3. Positive fusional vergence (PFV) blur: 12-week/ baseline mean PFV blur \>1.419 (Note: All 3 criteria must be met in order to be classified as an "improver" at the 12-week primary outcome visit).