Table 2.
Clinical trials in IRD using molecules with antioxidant, antiapoptotic, anti-inflammatory and/or visual cycle modulator properties.
| Compound | Mechanism | Disease | Participants (Number) |
Follow-Up Time | Trial ID | Phase/ Status |
References | Results |
|---|---|---|---|---|---|---|---|---|
|
N-acetylcysteine
(NAC) |
Antioxidant Stabilizes protein structure |
RP | 30 | 10 m |
NCT03063021 (FIGHT-RP) |
1/ Completed (2019) |
Campochiaro et al., 2020 and Kong et al., 2021 [121,122] |
NAC is safe and well-tolerated Improvement in macular functioning cones |
| NAC | RP | 30 | 6 m | NCT04864496 | 2/Active | |||
|
NACA
(NPI-001) |
Antioxidant Stabilizes protein structure |
Usher syndrome | 48 | 24 m |
NCT04355689 (SLO RP) |
1, 2/ Recruiting |
||
| Saffron | Neuroprotective and antioxidant effects | Stargardt Disease | 30 (31) | 6 m |
NCT01278277 (STARSAF02) |
1,2/ Unknown |
Piccardi et al., 2019 [427] | No detrimental effects on ERG and visual acuity |
| Minocyclin | Anti-inflammatory, antiapoptotic and neuroprotective effects |
RP | 35 | 24 wk | NCT04068207 | 2/ Recruiting |
||
| Minocyclin | Cystoid macular edema associated with RP | 7 | 12 m | NCT02140164 | 1, 2/ Completed (2015) |
Cukras et al., 2017 [428] |
Well tolerated. No significant changes in mean visual acuity. Small but progressive decrease in mean central macular thickness. | |
| Lutein | Removes ROS; protection against photo-oxidative stress |
RP | 34 | 48 wk | NCT00029289 | 1,2/ Completed (2008) |
Bahrami et al., 2006 [429] | Lutein supplementation improves visual field |
| Lutein in patients receiving vitamin A | RP | 240 | 5 yr | NCT00346333 | 3/ Completed (2008) |
Berson et al., 2010 [430] | 12 mg/d of lutein slows visual field loss among nonsmoking patients with RP with vitamin A | |
|
Lycium
barbarum |
Antioxidative, anti-inflammatory, and antiapoptotic mechanisms |
RP | 50 (42) | 1 yr | NCT02244996 | NA/ Completed (2017) |
Chan et al., 2019 and Vidović et al., 2022 [317] For review: [431] |
Preservation of photopic vision |
| 4-Phenylbutyric acid | ER stress-regulated transmembrane protein | Achromatopsia | 2 | 6 m | NCT04041232 | Early phase 1/ Not yet recruiting |
||
| Vitamin A | Improvement in cone photoreceptor function |
RP (RHO1 mutation) | 10 (5 RP) | 6 wk | NCT00065455 | 1/ Completed (2009) |
||
|
Vitamin A and/or
Vitamin E |
RP | 601 (572) | 4 yr. | NCT00000114 | 3/ Completed (1987) |
Berson et al., 1993 [425] | Beneficial effect of 15,000 IU/d of vitamin A Adverse effect of 400 IU/d of vitamin E |
|
| Vitamin A | RP | 5 yr | NCT00000116 | 3/ Completed (1997) |
||||
| Vitamin A | Choroideremia | 10 | 8 m | NCT05045703 (DARC) | Not yet recruiting | |||
| QLT091001 | Replaces chromophore in visual cycle | Leber congenital amaurosis (mutation RPE65, LRAT) | 32 | 12 m |
NCT01014052 (RET IRD 01) |
1b/ Completed (2012) |
Scholl H et al., 2015 [432] Wen & Birch 2015 [433] Koenekoop et al., 2014 [434] |
Improvements in visual field and/or visual acuity. Cortical activation |
|
QLT091001
(retreatment) |
Leber congenital amaurosis (mutation RPE65, LRAT) | 27 | 12 m |
NCT01521793 (RET IRD 01 extension) |
1/ Completed (2014) |
Scholl et al., 2015 [435] |
Sustained visual improvements | |
| QLT091001 | ADRP (RPE65 mutation) | 5 | 12 m | NCT01543906 | 1/ Completed (2014) |
|||
| ALK-001 | Chemically modified vitamin A (replacement of vitamin A) | Healthy volunteers |
40 | 4 wk | NCT02230228 | 1/ Completed |
||
| ALK-001 | Stargardt Disease |
140 | 24 m |
NCT02402660 (TEASE) |
2/ Recruiting |
|||
| ALK-001 | Stargardt Disease |
140 | 24 m |
NCT04239625 (TEASE-2, an open-label extension of TEASE) |
2/ Enrolling by invitation |
|||
| DHA (docosahexaenoic acid; omega 3) | Key cell membrane component involved in multiple metabolic pathways |
X-linked RP | 221 (208) | 4 yr | NCT00100230 | 2/ Completed (2014) |
Hoffman et al., 2014 [436] Hughbanks- Wheaton et al., 2014 [437] Hoffman et al., 2015 [438] |
|
| DHA | X-linked RP | 46 | 3 yr | NCT00004827 | 2/ Completed (2002) |
For review see: Schwartz et al., 2020 [422] | ||
| DHA | Usher Syndrome | 100 | NCT00004345 | NA/ Terminated |
||||
|
DHA in
patients receiving Vit A |
RP | 221 | 4 yr | NA | Berson et al., 2004 [439] Berson et al. 2004 [440] |
No improvement with DHA in patients with RP receiving Vit A 4 yr Improvements in the first 2 yr |
||
| DHA | Stargardt or Stargardt-like Macular Dystrophy |
22 | 15 m | NCT00060749 | 1/ Completed (2007) |
MacDonald & Sieving 2018 [441] | ||
| DHA | Stargardt and dry AMD | 32 | 24 wk |
NCT03297515 (MADEOS) |
NA/ Completed (2020) |
|||
| Hydroxychloroquine | Targets autophagy pathway |
P23H-RHO RP | 12 | 18 m | NCT04120883 | 1, 2/ Recruiting |
||
| 4-Methylpyrazole (4-MP) (alcohol dehydrogenase inhibitor) | Slows down processing of vitamin A derivatives |
Healthy volunteers |
10 | 6 wk | NCT00346853 | 1/ Completed |
Jurgensmeier et al., 2007 [442] | 4-MP does not inhibit human visual cycle sufficiently to be evaluated for Stargardt disease treatment |
| Emixustat | RPE65 inhibitor |
Stargardt | 23 | 1 m |
NCT03033108 (SeaSTAR) |
2A Dose scalation/ Completed (2017) |
No SAES Frequent ocular side effects |
|
| Emixustat | Stargardt | 194 | 2 yr | NCT03772665 | 3/Active | |||
| Soraprazan | H,K+-ATPase inhibitor Removes retinal lipofuscine accumulation |
Stargardt | 90 | 12 m | EudraCT 2018-001496-20 | 2/Active | ||
| Zimura (avacincaptad pegol) | Aptamer that inhibits the activity of complement factor C5 | Stargardt 1 | 120 | 18 m | NCT03364153 | 2b/ Recruiting |
||
| STG-001 | RBP4 antagonist Visual cycle regulator |
Stargardt 1 | 10 | 4 wk | NCT04489511 | 2a (2 doses)/ Completed (2021) |
||
| L-DOPA | Upregulates PDEF Downregulates VEGF |
RP | 50 | 5 yr | NCT02837640 | 2/NA | ||
| Valproic acid | Neuroprotective Induces microglial apoptosis |
ADRP | 90 | 52 wk | NCT01233609 | 2/ Completed (2015) |
Birch et al., 2018 [443] | No efficacy was found |
| Valproic acid | RP | 200 | 48 wk | NCT01399515 | 2/ Completed (2015) |
|||
|
Dunaliella
Bardawil powder (oral) |
Beta carotene | RP | 34 | 1 yr | NCT01256697 | NA/ Completed (2009) |
Rotenstreich et al., 2013 [444] | Increase retinal function in RP |
| Dunaliella Bardawil powder | RP in adolescents |
30 | 72 wk | NCT02018692 | 1, 2/Not yet recruiting | |||
| Dunaliella Bardawil powder | RP | 100 | 72 wk | NCT01680510 | 2, 3/ Recruiting |
|||
|
rhNGF
(recombinant human nerve growth factor) (drops) |
Neuroprotection | RP | 50 | 48 wk | NCT02110225 | 1, 2/ Completed (2015) |
||
| Cannabis (cannabidiol:THC, 1:1) | Neuroprotection | RP | 50 | 3 h. | NCT03078309 | 1/ Recruiting |
||
| NP-001 (oral) | Inactivates macrophages. Anti-inflammatory | Usher syndrome | 48 | 24 m. | NCT04355689 (SLO RP) | 1, 2/ Recruiting |
Abbreviations: RP, retinosis pigmentaria; ADRP, autosomal dominant retinosis pigmentaria; h, hour(s); wk, week(s); m, month(s); yr, year(s). Clinical trial information was retrieved from ClinicalTrials.gov (http://www.clinicaltrials.gov, accessed on 1 February 2022) and EU Clinical Trials Register (https://www.clinicaltrialsregister.eu/, accessed on 1 February 2022).