Systematic Review of Randomized Clinical Trials on Safety and Efficacy of Pharmacological and Nonpharmacological Treatments for Retinitis Pigmentosa

Table 1

Study design and characteristics of randomized clinical trials included in the systematic review.

Randomized clinical trial	Masking	Treatments	Treatment duration	Time-point evaluation
Chatzinoff et al. 1968 [28]	Double-masked, controlled	100.000 U 11-cis vitamin A IM twice weekly versus 100.000 all-trans vitamin A IM twice weekly	3 years	Every six months for the duration of the study
Newsome et al. 1987 [32]	Double-masked, placebo-controlled	Gangliosides 40 mg/2 mL/day IM versus 0.9% sodium chloride solution/day IM injection	4 months	Baseline, 4 months.
Berson et al. 1993 [8]	Double-masked trial with 2 × 2 factorial design	Vitamin A 15,000 IU/day + vitamin E 3 UI/day (grA), vitamin A 75 IU/day + vitamin E 400 IU/day (grE), or vitamin A 15,000 IU/day + vitamin E 400 IU/day (grA + E) versus trace amounts of both vitamin A (75 IU/day) and vitamin E (3 UI/day) (trace group)	4 to 6 years	Each year for the duration of the study
Sibulesky et al. 1999 [33]; Long term safety in the same population of Berson et al. 1993 [8]	Double-masked	Vitamin A 15,000 IU/day + vitamin E 3 UI/day (grA), vitamin A 75 IU/day + vitamin E 400 IU/day (grE), or vitamin A 15,000 IU/day + vitamin E 400 IU/day (grA + E) versus trace amounts of both vitamin A (75 IU/day) and vitamin E (3 UI/day) (trace group)	Up to 12 years	Baseline, 5 and 12 years
Vingolo et al. 1998 [6]	Unmasked study	Hyperbaric oxygen 90 min O2 daily 5 times a week for 1 month, 1 week a month for 11 months, and 1 week every 3 months for 2 years versus no hyperbaric oxygen	3 years	Each year for the duration of the study
Wheaton et al. 2003 [34]; Long term safety in the same population of Hoffman et al. 2004 [30]	Double-masked, placebo-controlled	Oral DHA 400 mg/day supplementation versus placebo	4 years	Every 6 months for the duration of the study
Berson et al. 2004 [27]	Double-masked, controlled	Fatty acids with DHA 1200 mg/day + vitamin A 15000 UI/day versus fatty acids + vitamin A 15000 UI/day	4 years	Each year for the duration of the study
Berson et al. 2004 [26] Subgroup analysis of Berson et al. 2004 [27]: patients taking vitamin A prior to entry versus patients not taking vitamin A prior to entry	Double-masked, controlled	Fatty acids with DHA 1200 mg/day + vitamin A 15000 UI/day versus fatty acids + vitamin A 15000 UI/day	4 years	Each year for the duration of the study
Hoffman et al. 2004 [30]	Double-masked, placebo-controlled	Oral DHA 400 mg/day supplementation versus placebo	4 years	Each year for the duration of the study
Bahrami et al. 2006 [9]	Double-masked, crossover	Lutein capsule 10 mg/day for 12 weeks and then 30 mg/day for 12 weeks + multivitamin supplementation versus placebo capsule + multivitamin supplementation	6 months	Baseline, 6, 12, 18, and 24 weeks
Merin et al. 2008 [14]	Double masked, controlled	Brimonidine tartrate 0.2% eye drops BID versus artificial tears BID	2-3 years (mean: 29.3 months)	Every 6–8 months for the duration of the study
Vingolo et al. 2008 [5]	Unmasked, controlled	Hyperbaric oxygen 90 min O2 daily 5 days a week for 1 month, 5 consecutive days a month for 11 months, and 5 consecutive days every 3 months for 9 years versus vitamin A	10 years	Every 6 months for the duration of the study
Berson et al. 2010 [10]	Double masked, controlled	12 mg oral lutein + vitamin A 15000 UI/day versus placebo + vitamin A 15000 UI/day	4 years	Each year for the duration of the study
Nakazawa et al. 2011 [13]	Nonmasked	Oral nilvadipine 4 mg/day versus tocopherol nicotinate 300 mg/day or helenien 15 mg/day or no treatments	30–66 months	Every 6 months for the duration of the study
Rotenstreich et al. 2013 [11]	Double-masked, placebo-controlled, crossover	Four capsule/day of 9-cis -carotene-rich alga Dunaliella bardawil (-carotene, approximately 20 mg) versus 4-day capsule of placebo	3 months of treatment, 3 months of washout, 3 months of crossover	Baseline, after 3 months of treatment, after 3 months of washout, and after 3 months of crossover treatment
Birch et al. 2013 [15]; Results of CNTF3 + CNTF4 studies	Masked, randomized, sham-controlled	High (20 ng/day) or low (5 ng/day) dose ciliary neurotrophic factor intraocular implant versus sham intraocular implant in the fellow eye	1 (CNTF3) or 2 years (CNTF4)	1 day, 1 week, 1, 3, 12, and 24 months, and follow-up up to 42 months
Hoffman et al. 2014 [29]	Double-masked, placebo-controlled	Multivitamin supplementation + DHA 30 mg/kg/day versus multivitamin supplementation + placebo capsules	4 years	Each year for the duration of the study
Hughbanks-Wheaton et al. 2014 [31]; Same population of Hoffman et al. 2014 [29]	Double-masked, placebo-controlled	Multivitamin supplementation + DHA 30 mg/kg/day versus multivitamin supplementation + placebo capsules	4 years	Each year for the duration of the study
Kumar et al. 2014 [12]	Data evaluators, masked	Oral valproic acid 500 mg/day versus no treatment	1 year	Baseline, 3, 6, and 12 months

BID: Twice daily.
QD: Once a day.
QID: Four times daily.