Evaluating the Effectiveness of Intravenous Immunoglobulin Therapy in Autoimmune Autonomic Ganglionopathy
Condition: Autoimmune Autonomic Ganglionopathy (AAG)
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      The purpose of the study is to see if administering intravenous immune globulin (IVIG)
      (putting immune globulin directly into your blood) helps to improve the symptoms of
      orthostatic hypotension (sudden fall in blood pressure when a person stands up) and quality
      of life in men and women who have autoimmune autonomic ganglionopathy (AAG).
    

Detailed description: 
      Autoimmune autonomic ganglionopathy (AAG) is a rare disease that results in severe
      dysautonomia (disorder of autonomic nervous system function). Many patients are unable to
      carry out activities of daily living due to autonomic symptoms that do not respond well to
      therapy (such as drops in blood pressure while standing). The recent discovery of antibodies
      that cause AAG has stimulated interest in immunomodulatory therapy (therapies that modify the
      functioning of the immune system). Studies in which a positive clinical response to these
      therapies have been reported in patients with AAG using immunomodulatory therapy as a
      treatment.

      The investigators plan to carry out a blinded, randomized trial using IVIG. There have been
      no reported randomized clinical trials with any immunosuppressive agent in AAG. The proposed
      studies, if successful, will provide the first reliable clinical evidence, that therapy with
      IVIG is an effective treatment of AAG.

      Treatment for the symptoms of autonomic failure is only effective in mild cases. Most
      patients require therapy that would change the course of the disease, but at present there is
      no established therapeutic regimen. The natural course of untreated AAG is not known.

      To address these unresolved issues, this clinical trial has the following goals:

        1. To measure the effect of IVIG treatment on orthostatic hypotension, autonomic symptoms
           and quality of life scores in patient participants with AAG.

        2. To determine the durability of IVIG (how long the treatment is effective) on orthostatic
           hypotension, autonomic symptoms and quality of life scores in patient participants with
           AAG.

      Participants enrolled in the study will receive two courses of intravenous immunoglobulin or
      placebo separated by 3 weeks. During the First Observation Period, participants will be
      evaluated after 6 weeks to determine the clinical response and natural history of the
      disorder.

      All the participants will then move to a single blinded second observation period.

      All patients enrolled in the study (IVIG group and placebo group) will receive two infusions
      of intravenous immunoglobulin, i.e., both cohorts will receive IVIG (although participants
      will not know this, and physicians will not be aware if this treatment is to IVIG naïve or
      IVIG continued participants).
    

Intervention name(s): Double blinded IVIg; Double blinded Placebo; Single Blinded IVIg
Intervention type(s): Drug; Other; Other
Intervention description(s): Participants will receive study treatment with IVIg, at 2.0 gm/kg over 2-4 consecutive days. A maintenance study treatment IVIg, at 1.0 gm/kg, over 1-2 consecutive days will occur three weeks later. All participants will proceed to the single blind Second Observation Period.; Participants will receive placebo (5% albumin) at 2.0 gm/kg over 2-4 consecutive days. A maintenance treatment with placebo (5% albumin) at 1.0 gm/kg, over 1-2 consecutive days will occur three weeks later. All participants will proceed to the single blind Second Observation Period.; This is the single blind Second Observation Period. All participants will receive study treatment with IVIg, at 2.0 gm/kg over 2-4 consecutive days. A maintenance study treatment at 1.0 gm/kg, over 1-2 consecutive days will occur three weeks later.
Other intervention name(s): Gammagard
Intervention MeSH terms: Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Autoimmune autonomic neuropathy; Orthostatic hypotension; Dysautonomia; Autonomic failure; Peripheral autonomic neuropathy