Status:

COMPLETED

Evaluating the Effectiveness of Intravenous Immunoglobulin Therapy in Autoimmune Autonomic Ganglionopathy

Lead Sponsor:

Beth Israel Deaconess Medical Center

Collaborating Sponsors:

Mayo Clinic

Vanderbilt University

Conditions:

Autoimmune Autonomic Ganglionopathy (AAG)

Eligibility:

All Genders

18-85 years

Phase:

PHASE2

PHASE3

Brief 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 (sudd...

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 dai...

Eligibility Criteria

Inclusion

  • Participants aged 18 to 85
  • Participants have neurogenic orthostatic hypotension (fall in systolic blood pressure \> 30 mmHg).
  • Symptoms of orthostatic intolerance.
  • Antibodies to the neuronal AChR of the autonomic ganglia of \>0.2nmol/l. Results must be within 6 months of the screening visit and there may not have been any immunomodulatory interventions since the time of the antibody measurement or the sample will need to be reconfirmed at screening.
  • Participants must be willing to withdraw from medications that affect vasoactive and autonomic function for 5 half-lives during testing (with the exception of stable doses of fludrocortisone up to 0.2 mg/day) and adhere to a regular diet

Exclusion

  • Women of childbearing potential (WOCP) who are not using a medically accepted contraception
  • Pregnant or lactating females- if participants become pregnant during the trial they will no longer receive IVIG, but will be followed as part of the intention to treat protocol.
  • Severe depression and/or anxiety (score of \> 29 on the Beck Depression Inventory or score on the Beck Anxiety Inventory of ≥ 36)
  • Active psychosis is ineligible, history of psychosis will be eligible, but only after review with the patients PCP and/or treating mental health provider.
  • History of asthma
  • Other causes of autonomic failure (e.g., diabetes, amyloidosis)
  • History of allergic or anaphylactic reaction to humanized or murine antibodies.
  • History or presence of recurrent or chronic infection (recurrent infections defined as \>4 times per year).
  • History of cancer, including solid tumors and hematologic malignancies (except fully resolved and resected cutaneous basal cell and squamous cell carcinomas of the skin)
  • History or presence of vascular disease potentially affecting brain or spinal cord (e.g., stroke, transient ischemic attack, carotid stenosis (greater than 80%), aortic aneurysm, intracranial aneurysm, hemorrhage, arteriovenous malformation)
  • History of severe, clinically significant central nervous system trauma (e.g., cerebral contusion, spinal cord compression)
  • History or presence of infectious causes of encephalopathy or myelopathy (e.g., syphilis, Lyme disease, human T-cell lymphotropic virus type 1 \[HTLV-1\], herpes zoster myelopathy)
  • History of thromboembolic events or deep vein thrombosis
  • Platelet count \<100,000/mL, Hemoglobin \<8.5 g/dL, Neutrophils \<1.5 x 103/mL.
  • Serum IgA deficiency: Immunoglobulin A (IgA) level \< 7 mg/dL.
  • History of immunosuppression or HIV/AIDS
  • History of cardiac arrhythmia or angina, electrocardiogram (ECG) showing significant abnormality that the treating investigator determines may jeopardize the participant's health (i.e., acute ischemia, left bundle branch, or bifascicular block)
  • History of renal failure or creatinine \>2.0
  • History of previous allergic response to albumin.
  • Treatment with IVIG or plasma exchange within 6 weeks of study enrollment.
  • Active adjustments of other immunomodulatory treatments. Patients that are on stable doses of immunomodulatory medications (no dose changes within 4 months -including, but not limited to prednisone, mycophenolate mofetil or azathioprine) but still have elevated antibody titers and meet criteria for inclusion will be allowed to participate in the study.

Key Trial Info

Start Date :

February 1 2012

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

September 1 2015

Estimated Enrollment :

6 Patients enrolled

Trial Details

Trial ID

NCT01522235

Start Date

February 1 2012

End Date

September 1 2015

Last Update

July 2 2017

Active Locations (6)

Enter a location and click search to find clinical trials sorted by distance.

Page 1 of 2 (6 locations)

1

Nih Ninds

Bethesda, Maryland, United States, 20895

2

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States, 02215

3

Mayo Clinic

Rochester, Minnesota, United States, 55905

4

NYU Medical Center

New York, New York, United States, 10016