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Trial record 1 of 1 for:    01233609
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Trial of Oral Valproic Acid for Retinitis Pigmentosa (VPA)

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ClinicalTrials.gov Identifier: NCT01233609
Recruitment Status : Completed
First Posted : November 3, 2010
Results First Posted : December 2, 2017
Last Update Posted : December 2, 2017
Sponsor:
Collaborator:
United States Department of Defense
Information provided by (Responsible Party):
Foundation Fighting Blindness

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Retinitis Pigmentosa
Interventions Drug: Valproic Acid
Drug: Placebo
Enrollment 90
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Valproic Acid Placebo
Hide Arm/Group Description

Subjects who receive valproic acid

Valproic Acid: One to four 250mg softgels by mouth daily (dose determined by body weight)

Subjects who receive placebo

Placebo: Dosage per subject weight- same schedule as the active comparator
Period Title: Overall Study
Started 46 44
Completed 37 42
Not Completed 9 2
Reason Not Completed
Death             1             0
Lost to Follow-up             3             1
Adverse Event             2             1
Withdrawal by Subject             3             0
Arm/Group Title Placebo Valproic Acid Total
Hide Arm/Group Description

Subjects who receive placebo

Placebo: Dosage per subject weight- same schedule as the active comparator

Subjects who receive valproic acid

Valproic Acid: One to four 250mg softgels by mouth daily (dose determined by body weight)

 Total of all reporting groups
Overall Number of Baseline Participants 44 46 90
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 44 participants 46 participants 90 participants
51.6  (10.9) 49.3  (12.3) 50.4  (11.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 46 participants 90 participants
Female
20
  45.5%
24
  52.2%
44
  48.9%
Male
24
  54.5%
22
  47.8%
46
  51.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 46 participants 90 participants
Hispanic or Latino
6
  13.6%
5
  10.9%
11
  12.2%
Not Hispanic or Latino
38
  86.4%
41
  89.1%
79
  87.8%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 46 participants 90 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
1
   2.2%
1
   1.1%
White
43
  97.7%
44
  95.7%
87
  96.7%
More than one race
0
   0.0%
1
   2.2%
1
   1.1%
Unknown or Not Reported
1
   2.3%
0
   0.0%
1
   1.1%
Genetic Mutations   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 44 participants 46 participants 90 participants
RHO
22
  50.0%
19
  41.3%
41
  45.6%
PRPF31
5
  11.4%
9
  19.6%
14
  15.6%
RP1
4
   9.1%
9
  19.6%
13
  14.4%
PRPF8
3
   6.8%
1
   2.2%
4
   4.4%
PRPH2
2
   4.5%
2
   4.3%
4
   4.4%
NR2E3
0
   0.0%
2
   4.3%
2
   2.2%
RHO and PRPH2
2
   4.5%
0
   0.0%
2
   2.2%
SNRNP200/ASCC3L1
2
   4.5%
0
   0.0%
2
   2.2%
TOPORS
0
   0.0%
2
   4.3%
2
   2.2%
IMPDH1
1
   2.3%
0
   0.0%
1
   1.1%
KLHL7
1
   2.3%
0
   0.0%
1
   1.1%
NR2E3 and TOPORS
0
   0.0%
1
   2.2%
1
   1.1%
RHO and ROM1
0
   0.0%
1
   2.2%
1
   1.1%
[1]
Measure Description: Summary of participants' gene mutation or combination of mutations identified and thought to be responsible for autosomal dominant retinitis pigmentosa
1.Primary Outcome
Title Mean Change in Visual Field Area From Baseline to 52 Weeks--III4e Isopter
Hide Description Mean change in visual field area from baseline to 52 weeks. Visual field area is measured with semi-automated kinetic perimetry (SKP) using the Octopus 900 (Haag-Streit) with the III4e target size for each eye and done at least twice to ensure reliable sessions; the visual field area measurements are averaged over the two sessions. Analysis performed with linear mixed model
Time Frame baseline to week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis followed the intent-to-treat principle in that all randomized participants were included and analyzed according to their treatment assignment regardless of amount or type of treatment received. Only observed data were analyzed.
Arm/Group Title Placebo--Right Eye Placebo--Left Eye Valproic Acid--Right Eye Valproic Acid--Left Eye
Hide Arm/Group Description:
Right eye of Placebo-treated patients
Left eye of Placebo-treated patients
Right eye of Valproic acid-treated patients
Left eye of Valproic acid-treated patients
Overall Number of Participants Analyzed 42 42 38 38
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
 42 42 38 38
Mean (Standard Deviation)
Unit of Measure: Visual field area (degrees squared)
-122.9  (543.60) -112.0  (584.63) -293.7  (736.56) -237.1  (691.76)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo--Right Eye, Placebo--Left Eye, Valproic Acid--Right Eye, Valproic Acid--Left Eye
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.035
Comments [Not Specified]
Method Mixed Models Analysis
Comments degrees of freedom = 830
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -150.43
Parameter Dispersion
Type: Standard Error of the Mean
Value: 71.37
Estimation Comments Right eye and Left Eye within each of the 2 treatment groups (Placebo and Valproic Acid) were combined to estimate the difference
2.Secondary Outcome
Title Mean Change in Visual Field Area From Baseline to 52 Weeks--I4e Isopter
Hide Description Mean change in visual field area from baseline to 52 weeks. Visual field area is measured with semi-automated kinetic perimetry (SKP) using the Octopus 900 (Haag-Streit) with the I4e target size for each eye and done at least twice to ensure reliable sessions; the visual field area measurements are averaged over the two sessions. Analysis performed with linear mixed model
Time Frame baseline to week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis followed the intent-to-treat principle in that all randomized participants were included and analyzed according to their treatment assignment regardless of amount or type of treatment received. Only observed data were analyzed.
Arm/Group Title Placebo--Right Eye Placebo--Left Eye Valproic Acid--Right Eye Valproic Acid--Left Eye
Hide Arm/Group Description:
Right eye of Placebo-treated patients
Left eye of Placebo-treated patients
Right eye of Valproic acid-treated patients
Left eye of Valproic Acid-treated patients
Overall Number of Participants Analyzed 42 42 38 38
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
 42 42 38 38
Mean (Standard Deviation)
Unit of Measure: Visual field area (degrees squared)
80.9  (406.2) 115.7  (696.89) 5.3  (759.46) 19.5  (703.83)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo--Right Eye
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.581
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
3.Secondary Outcome
Title Static Perimetry by Treatment Arm--Full Field Hill of Vision
Hide Description Mean change from baseline at week 52 for Full field Hill of Vision (Static perimetry)
Time Frame baseline to week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis followed the intent-to-treat principle in that all randomized participants were included and analyzed according to their treatment assignment regardless of amount or type of treatment received. Only observed data were analyzed.
Arm/Group Title Placebo--Right Eye Placebo--Left Eye Valproic Acid--Right Eye Valproic Acid--Left Eye
Hide Arm/Group Description:
Right eye of Placebo-treated patients
Left eye of Placebo-treated patients
Right eye of Valproic acid-treated patients
Left eye of Valproic acid-treated patients
Overall Number of Participants Analyzed 41 41 39 39
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
 41 41 39 39
Mean (Standard Deviation)
Unit of Measure: db-steridians
-0.3  (2.55) -1.4  (3.27) -0.2  (5.11) -0.6  (4.68)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo--Right Eye
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.409
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
4.Secondary Outcome
Title Static Perimetry Volume--30 Degree Hill of Vision
Hide Description Mean Change from baseline to week 52 for Static Perimetry Volume --30 Degree Hill of Vision. Full field static perimetry protocol was followed using the Octopus 900 (Haag-Streit) for a single session for each eye.
Time Frame baseline to week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis followed the intent-to-treat principle in that all randomized participants were included and analyzed according to their treatment assignment regardless of amount or type of treatment received. Only observed data were analyzed.
Arm/Group Title Placebo--Right Eye Placebo--Left Eye Valproic Acid--Right Eye Valproic Acid--Left Eye
Hide Arm/Group Description:
Right eye of placebo-treated patients
Left eye of Placebo-treated patients
Right eye of Valproic acid-treated patients
Left eye of Valproic Acid-treated patients
Overall Number of Participants Analyzed 41 41 39 39
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
 41 41 39 39
Mean (Standard Deviation)
Unit of Measure: db-steridans
-0.3  (0.61) -0.3  (0.73) -0.2  (1.07) -0.2  (0.96)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo--Right Eye
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.229
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
5.Secondary Outcome
Title Mean Change From Baseline in Best Corrected Visual Acuity
Hide Description Mean change in best corrected visual acuity as assessed by ETDRS (Early Treatment Diabetic Retinopathy Study) method from baseline to week 52
Time Frame baseline to week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis followed the intent-to-treat principle in that all randomized participants were included and analyzed according to their treatment assignment regardless of amount or type of treatment received. Only observed data were analyzed.
Arm/Group Title Valproic Acid -- Right Eye Valproic Acid--Left Eye Placebo --Right Eye Placebo --Left Eye
Hide Arm/Group Description:
Results from the Right Eye in Patients treated with Valproic Acid
Results from the Left Eye in Patients treated with Valproic Acid
Results from the Right Eye in Patients treated with Placebo
Results from the Left Eye in Patients treated with Placebo
Overall Number of Participants Analyzed 40 40 42 42
Mean (Standard Deviation)
Unit of Measure: letters read correctly
-1.4  (5.21) 0.0  (3.41) 0.2  (4.41) 1.3  (5.05)
Time Frame Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Valproic Acid
Hide Arm/Group Description

Subjects who receive placebo

Placebo: Dosage per subject weight- same schedule as the active comparator

Subjects who receive valproic acid

Valproic Acid: One to four 250mg softgels by mouth daily (dose determined by body weight)
All-Cause Mortality
Placebo Valproic Acid
Affected / at Risk (%) Affected / at Risk (%)
Total   0/44 (0.00%)   1/46 (2.17%) 
Hide Serious Adverse Events
Placebo Valproic Acid
Affected / at Risk (%) Affected / at Risk (%)
Total   2/44 (4.55%)   3/46 (6.52%) 
Cardiac disorders     
Atrial Fibrilation * 1  1/44 (2.27%)  0/46 (0.00%) 
Eye disorders     
Lens Dislocation * 1  1/44 (2.27%)  0/46 (0.00%) 
Immune system disorders     
Immunodeficiency common variable † 1 [1]  0/44 (0.00%)  1/46 (2.17%) 
Injury, poisoning and procedural complications     
Road Traffic Accidents * 1 [2]  0/44 (0.00%)  1/46 (2.17%) 
Musculoskeletal and connective tissue disorders     
Osteoarthritis * 1  0/44 (0.00%)  1/46 (2.17%) 
1
Term from vocabulary, MedDRA (19.0)
*
Indicates events were collected by non-systematic assessment
†
Indicates events were collected by systematic assessment
[1]
Common Variable Immune Deficiency
[2]
Motorcycle crash
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Valproic Acid
Affected / at Risk (%) Affected / at Risk (%)
Total   41/44 (93.18%)   45/46 (97.83%) 
Eye disorders     
Vision Blurred * 1  5/44 (11.36%)  3/46 (6.52%) 
Cystoid Macular Oedema * 1  1/44 (2.27%)  3/46 (6.52%) 
Gastrointestinal disorders     
Nausea * 1  3/44 (6.82%)  8/46 (17.39%) 
Dyspepsia * 1  0/44 (0.00%)  8/46 (17.39%) 
Diarrhea * 1  1/44 (2.27%)  4/46 (8.70%) 
Abdominal Pain Upper * 1  2/44 (4.55%)  3/46 (6.52%) 
Gastroesophageal Reflux Disease * 1  0/44 (0.00%)  3/46 (6.52%) 
General disorders     
Fatigue * 1  3/44 (6.82%)  6/46 (13.04%) 
Infections and infestations     
Nasopharyngitis * 1  9/44 (20.45%)  3/46 (6.52%) 
Sinusitis * 1  3/44 (6.82%)  7/46 (15.22%) 
Influenza * 1  7/44 (15.91%)  1/46 (2.17%) 
Bronchitis * 1  0/44 (0.00%)  3/46 (6.52%) 
Investigations     
Ammonia Increased † 1  1/44 (2.27%)  7/46 (15.22%) 
Alanine Aminotransferase Increased † 1  2/44 (4.55%)  3/46 (6.52%) 
Aspartate Aminotransferase Increased † 1  1/44 (2.27%)  3/46 (6.52%) 
Weight Increased * 1  0/44 (0.00%)  4/46 (8.70%) 
Hepatic Enzyme Increased † 1  0/44 (0.00%)  3/46 (6.52%) 
Nervous system disorders     
Headache * 1  4/44 (9.09%)  8/46 (17.39%) 
Dizziness * 1  3/44 (6.82%)  2/46 (4.35%) 
Tremor * 1  0/44 (0.00%)  3/46 (6.52%) 
1
Term from vocabulary, MedDRA (19.0)
*
Indicates events were collected by non-systematic assessment
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Drug Development Officer
Organization: Foundation Fighting Blindness Clinical Research Institute
Phone: 410 423 0581
EMail: pzilliox@blindness.org
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Foundation Fighting Blindness
ClinicalTrials.gov Identifier: NCT01233609    
Other Study ID Numbers: H-13371
First Submitted: November 1, 2010
First Posted: November 3, 2010
Results First Submitted: August 17, 2017
Results First Posted: December 2, 2017
Last Update Posted: December 2, 2017