Effect of six months intravenous immunoglobulin treatment on brain glucose metabolism in patients with mild to moderate Alzheimer’s disease: A phase II double blind, placebo-controlled multi-center study

Objectives Octagam® 10% is a human immunoglobulin solution ready for intravenous administration (IVIG) first developed for treating immune deficiency. We now assess the effect of six months treatment with IVIG versus placebo on cerebral glucose metabolism in patients with Alzheimer’s disease (AD).

Methods 58 patients with mild to moderate AD were included in this study, of whom 55 patients received a baseline [18F]FDG PET scan and MRI. This was followed by treatment with Octagam® 10% over 24 weeks, consisting of either (1) six infusions at 4-week intervals of 0.2 g/kg, 0.5 g/kg or 0.8 g/kg Octagam® 10% or (2) 12 infusions at 2-week intervals (0.1 g/kg, 0.25 g/kg, and 0.4 g/kg body weight Octagam® 10%) (3) or corresponding placebo. After 6 months, 44 patients received a follow-up [18F]FDG PET scan. PET scans were both analyzed using region of interest analyses and statistical parametric mapping.

Results Using an ROI-based approach, patients receiving placebo showed a significant decrease of glucose metabolism in temporal brain regions in six months (- 4.9%; p<0.005). The IGIV-treated patients did not show a significant decrease in this brain region (- 1%; n.s.) and furthermore displayed in the voxel-based approach a significantly increased glucose metabolism in widespread parietal and frontal brain regions at follow-up (p<0.05, FDR-corrected).

Conclusions Treatment of mild to moderate AD patients with Octagam® for six months attenuated the decline in cerebral glucose metabolism seen in the temporal lobe of the placebo group. The active drug group also had a significant increase in FDG uptake in parietal and frontal cortex. These observations corroborate earlier findings with IVIG in AD and encourage conducting further studies in a larger patient cohort.

Research Support This study is part of a research project sponsored by Octapharma AG