A double blind-placebo controlled trial of IVIG in the treatment of AAG: Results, Implications and Lessons Learned (S12.003)

Objective: To determine the utility of IVIG for the treatment of autonomic dysfunction in autoimmune autonomic ganglionopathy (AAG). Background: AAG is a rare disease with no established evidence-based treatment. Design/Methods: Subjects underwent a 6-week double-blind, placebo-controlled trial of IVIG for AAG, with a 6 week single blind extension. Comprehensive autonomic assessment was performed before and after treatment. Results: Recruitment for the study was challenging and only 5 subjects completed the study: 2 received IVIG and 3 received placebo. Due to small numbers of participants, the results were not statistically significant. The treated group had a mean systolic blood pressure improvement in orthostatic hypotension of 33+/−29 mmHg compared to the placebo treated group that had a 5.5+/−4.5 mmHg worsening in orthostatic hypotension. There was a modest improvement in autonomic symptom score (COMPASS) in the IVIG group of 3.3+/−2.8 points, and an improvement in the placebo group of 0.5+/−5.1 points. There was no change in sudomotor or parasympathetic function during the trial in either group. The CASS score was 9–10 at baseline and did not change with IVIG or placebo despite the change in orthostatic hypotension. Conclusions: Although this treatment trial did not meet targeted enrollment, a number of important lessons were learned. IVIG improved orthostatic hypotension, the primary endpoint of treatment, and modestly improved autonomic symptoms. Despite this, there was no difference in CASS scores. This may be a reflection of the effects of this specific intervention on parasympathetic and sympathetic cholinergic function, the assay sensitivity of CASS in severe autonomic failure and/or the lack of power in the study. These findings should be considered in the design of future trials. Study Supported by: Study supported by NIH U54 NS065736. Disclosure: Dr. Gibbons has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Lundbeck Inc. Dr. Rajan has nothing to disclose. Dr. Garcia Perez has nothing to disclose. Dr. Robertson has nothing to disclose. Dr. Biaggioni has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Lundbeck Inc. Dr. Kaufmann has received personal compensation in an editorial capacity for Lundbeck Inc. Dr Peltier has nothing to disclose. Dr. Vernino has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Lundbeck, Quest. Dr. Low has nothing to disclose. Dr. Freeman has nothing to disclose.