Table 1.
Summary of results in Charcot-Marie-Tooth type 1A (CMT1A)
| Gene, | Title | First Author, | Phenotype | Study | Number of | Drug | Duration | Target effect | Clinical effect | JADAD | OCEBM | UK | ||
| Mutation | Journal | target HPO | type | patients | name | (+/– / =), | (+/– / =), | score | score | License | ||||
| (Year) | term(s) | description | description | (1– 5) | (1– 5) | (Y/N) | ||||||||
| PMP22, dup | Ascorbic acid for CMT type 1A in children: a randomised, double-blind, placebo-controlled, safety and efficacy trial | Burns, Lancet Neurol (2009) [30] | Abnormal nerve conduction velocity | RCT | 81 (42 intervention, 39 placebo) | Ascorbic acid | 1 year | + | ↑plasma ascorbic acid concentration | = | No significant change in median NCV, strength, function, or QoL | 5 | 2 | *N |
| PMP22, dup | Effect of ascorbic acid in patients with CMT type 1A: a multicentre, randomised, double-blind, placebo-controlled trial | Micallef, Lancet Neurol (2009) [36] | Muscle weakness, Distal sensory impairment | RCT | 179 (intervention 61 dose 3 g, 56 dose 1 g, 62 placebo) | Ascorbic acid | 1 year | Not described | = | No significant change in CMTNS | 5 | 2 | *N | |
| PMP22, dup | Oral high dose ascorbic acid treatment for one year in young CMT1A patients: a randomised, double-blind, placebo-controlled phase II trial | Verhamme, BMC Med (2009) [37] | Muscle weakness, Distal sensory impairment | RCT | 13 (6 intervention, 7 placebo) | Ascorbic acid | 1 year | Not described | = | No significant change in median NCVs, strength, sensation, CMTNS or disability | 5 | 2 | *N | |
| PMP22, dup | Randomised controlled trial with ascorbic acid in CMT type 1A: results of the CMT-TRIAAL/CMT-TRAUK Ascorbic Acid in Charcot-Marie-Tooth Disease Type 1A (CMT-TRIAAL and CMT-TRAUK): A Double-Blind Randomised Trial | Pareyson, JPNS (2011) Pareyson, Lancet neurol (2011) [36] | Muscle weakness, Distal sensory impairment | RCT | 277 (138 intervention, 133 placebo) | Ascorbic acid | 24 months | Not described | = | No significant change in CMTNS | 5 | 2 | *N | |
| PMP22, dup | High-dosage ascorbic acid treatment in CMT type 1A: results of a randomized, double-masked, controlled trial | Lewis, JAMA Neurol (2013) [37] | Muscle weakness, Distal sensory impairment | RCT | 85 (69 intervention, 16 placebo) | Ascorbic acid | 2 years | = | No change in PMP22 mRNA levels | = | No significant change in CMTNS | 5 | 2 | *N |
| PMP22, dup | Phase II, Randomized, Placebo-controlled Trial in Patients With CMT type 1A | ClinicalTrials.gov Identifier: NCT01401257 (2017) [38] | Muscle weakness, Distal sensory impairment | RCT | 80 | PXT3003 | 12 months | Not described | + | Decreased CMTNS &ONLS in high dose group | 5 | 2 | N | |
| PMP22, dup | A multicenter, double-blind, placebo controlled, pivotal phase III study (PLEOCMT) of a fixed combination of baclofen, naltrexone and sorbitol (PXT3003), for the treatment of CMT1A | Attarian, Muscle &nerve (2017) NCT02579759 (2020) [39] | Muscle weakness, Distal sensory impairment | RCT | 323 | PXT3003 | 15 months | Not described | +/= | Significant ↓ONLS for dose 2, non-significant ↓ONLS for dose 1 | 5 | 2 | N | |
| PMP22, dup | Effects of exercise and creatine on myosin heavy chain isoform composition in patients with Charcot-Marie-Tooth disease | Smith, Muscle Nerve (2006) [40] | Muscle weakness | RCT | 18 | Creatine monohydrate + resistance training | 12 weeks | + | Significant decrease in MHC type I | + | ↓Chair-rise-time, ↑muscle strength | 5 | 2 | N |
Summary of results in Charcot-Marie-Tooth type 1A (CMT1A). Key: + positive change, - negative change, = no change, NCV nerve conduction velocity, RCT randomised controlled trial, CMTNS Charcot-Marie-Tooth Neuropathy Score, ONLS Overall Neuropathy Limitations Scale, QoL Quality of Life, *Licensed for other indication.