Recombinant human growth hormone for remyelination in MS: Results of a pilot trial in patients with chronically delayed VEP (P5.344)

Objective: To exclude major increase of inflammatory activity by rhGH treatment in MS; to explore a potential remyelinating effect. Background: Remyelination in MS is unpredictable and inefficient; it appears limited primarily by failure of oligodendrocyte progenitor (OPC) maturation. Insulin-like growth factor-1 (IGF-1) accelerates OPC maturation; it is induced by recombinant human growth hormone (rhGH). RhGH has immunostimulatory effects and may increase inflammatory activity in MS. Design/Methods: Single-cross-over open trial, including MS patients with chronically delayed visual evoked potential (VEP) in at least one eye. 4-weekly Gd-cMRI from weeks −12 to 12; VEP at weeks −12, 0, 12 and 24; daily s.c. rhGH from week 0 to 24, dosage adjusted until week 10, targeting plasma IGF-1 above reference. Primary endpoint: ratio of cumulative new active lesions (CNAL) during weeks 4 to 12 (CNAL_treat) over weeks −8 to 0 (CNAL_base); a maximum ratio of 2 was regarded acceptable. Results: Twenty-five patients completed the treatment period; 19/25 reached target IGF-1 plasma concentrations by week 10. Eighteen and 12 patients had no active lesions during baseline and treatment periods, respectively. Mean CNAL_base was 0.68, and CNAL_treat 1.24, yielding a ratio of 1.82 (95%CI 0.72–2.92); mean difference CNAL_treat – CNAL_base was 0.56 (95%CI −0.24–1.36). Mean change of VEP P100 latency from baseline to week 24 was +2.27msec (95%CI −3.81 to +8.34; p=0.16, one-sample t-test), irrespective of achieved IGF-1 plasma concentrations. Conclusions: RhGH did not induce a major increase of inflammatory activity. However, the point estimate of the CNAL_treat over CNAL_base ratio is just below the prespecified tolerance limit of 2, which is not excluded from the 95%CI. Chronically delayed VEP latencies did not improve. Further analyses of MRI measures of brain myelin content are ongoing, including acute effects in active lesions. Study Supported by: German Federal Ministry of Education and Research, through TRM Leipzig (BMBF, 1315883). Drug donation by Pfizer Pharma GmbH. Disclosure: Dr. Stoppe has nothing to disclose. Dr. Ettrich has nothing to disclose. Dr. Thomae has nothing to disclose. Dr. Lobsien has nothing to disclose. Dr. Kratzsch has nothing to disclose. Dr. Hasenclever has nothing to disclose. Dr. Then Bergh has received personal compensation for activities with Bayer, Biogen Idec, Genzyme-Sanofi, Novartis, and Roche as a speaker or member of an advisory board. Dr. Then Bergh has received research support from Actelion and Novartis.