Contributions
Abstract: P1184
Type: Poster
Abstract Category: Therapy - disease modifying - 27 Neuroprotection and Repair
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.
Objective: To exclude major increase of inflammatory activity by rhGH treatment in MS; to explore a potential remyelinating effect.
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. The validity of this observation may be limited by the substantial number of patients not contributing active lesions. Chronically delayed VEP latencies did not improve; further analyses of MRI measures of brain myelin content are ongoing, including in active lesions.
Disclosure: Study Supported by: German Federal Ministry of Education and Research, through TRM Leipzig (BMBF, 1315883). Drug donation by Pfizer GmbH Deutschland.
Potential conflicts of interest not related to this abstract within the past year before abstract submission:
FTB received funding from the DFG; received, through his institution, research support for investigator-initiated studies from Actelion and Novartis; has served on scientific advisory boards for Novartis, Sanofi/Genzyme and Roche; has received support to attend a scientific meeting from Biogen; and has received personal honoraria for speaking from Sanofi/Genzyme and Bayer Schering, Biogen, Roche and Sanofi/Genzyme. MS has received, through her institution, research support from Novartis, and support to attend scientific meetings from Novartis.
Abstract: P1184
Type: Poster
Abstract Category: Therapy - disease modifying - 27 Neuroprotection and Repair
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.
Objective: To exclude major increase of inflammatory activity by rhGH treatment in MS; to explore a potential remyelinating effect.
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. The validity of this observation may be limited by the substantial number of patients not contributing active lesions. Chronically delayed VEP latencies did not improve; further analyses of MRI measures of brain myelin content are ongoing, including in active lesions.
Disclosure: Study Supported by: German Federal Ministry of Education and Research, through TRM Leipzig (BMBF, 1315883). Drug donation by Pfizer GmbH Deutschland.
Potential conflicts of interest not related to this abstract within the past year before abstract submission:
FTB received funding from the DFG; received, through his institution, research support for investigator-initiated studies from Actelion and Novartis; has served on scientific advisory boards for Novartis, Sanofi/Genzyme and Roche; has received support to attend a scientific meeting from Biogen; and has received personal honoraria for speaking from Sanofi/Genzyme and Bayer Schering, Biogen, Roche and Sanofi/Genzyme. MS has received, through her institution, research support from Novartis, and support to attend scientific meetings from Novartis.