Autoimmune Autonomic Ganglionopathy (AAG)Phase 2/3NCT01522235

Evaluating the Effectiveness of Intravenous Immunoglobulin Therapy in Autoimmune Autonomic Ganglionopathy

A Phase 2/3 study testing Double blinded IVIg and Single Blinded IVIg in people with Autoimmune Autonomic Ganglionopathy (AAG), run by Beth Israel Deaconess Medical Center at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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… Read more about this study

Who is it for?: Ages 18 to 85 years
Conditions the study is for: Autoimmune Autonomic Ganglionopathy (AAG)
What is being tested?: Double blinded IVIg and Single Blinded IVIg
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 6 participants
Where: 6 sitesUnited States
Study dates: Feb 2012to Sep 2015
Phase: Phase 2/3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 85 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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)

Show all 21Show fewer

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.

Trial locations and contacts

6 sites in 1 country.

City, postcode or hospital

6 sites in 1 country

United States6 sites

Nih Ninds
Bethesda, Maryland, 20895
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
UT Southwestern Medical Center
Dallas, Texas, 75390
Vanderbilt University
Nashville, Tennessee, 37215
NYU Medical Center
New York, New York, 10016
Mayo Clinic
Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: A Double-blind, Randomized, Placebo-controlled Trial to Evaluate the Efficacy of Intravenous Immunoglobulin Therapy in Autoimmune Autonomic Ganglionopathy.

Read the 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:

To measure the effect of IVIG treatment on orthostatic hypotension, autonomic symptoms and quality of life scores in patient participants with AAG.
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).

Conditions: Autoimmune Autonomic Ganglionopathy (AAG)
Being tested: Double blinded IVIg, Double blinded Placebo, Single Blinded IVIg
Keywords: Autoimmune autonomic neuropathy, Orthostatic hypotension, Dysautonomia, Autonomic failure, Peripheral autonomic neuropathy
Medical subject headings: Hypotension, Orthostatic, Autonomic Nervous System Diseases, Pure Autonomic Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Double blinded IVIgDrug
Also called Gammagard
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.
Double blinded PlaceboOther
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.
Single Blinded IVIgOther
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.

Study groups in NCT01522235
Study group	Role	What they receive
IVIg group	Active comparator	Double blinded IVIg and single blinded IVIg Receives: Drug: Double blinded IVIg; Other: Single Blinded IVIg
Placebo Group	Other	Double blinded Placebo and single blinded IVIg Receives: Other: Double blinded Placebo; Other: Single Blinded IVIg

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Systolic Blood Pressure During 60° Tilt (ΔSBP)
The primary outcome, the change in systolic blood pressure during 60 degree tilt (ΔSBP), will be assessed in all study participants at baseline and at 6 weeks.
Measured: Baseline and 6 weeks

Secondary outcomes (5)

Change in Systolic Blood Pressure During 60° Tilt (ΔSBP)
To compare the change in systolic blood pressure during 60 degree head up tilt table test after 6 and 12 weeks of IVIG (the within-patient difference in ΔSBP at 12 and 6 weeks among treated patients).
Measured: 6 weeks and 12 weeks
Composite Autonomic Symptom Score [COMPASS] Questionnaire
To determine the change in autonomic symptoms (measured by the composite autonomic symptom score [COMPASS] questionnaire) measured at baseline and 6 weeks. Minimum and maximum score possible: 0-100. We have reported the Total score. Higher values represent worse outcome.
Measured: Baseline, 6 weeks
Composite Autonomic Severity Score (CASS) Questionnaire.
To determine the change in autonomic symptoms (measured by the composite autonomic severity score [CASS]) measured at baseline and 6 weeks in individuals receiving IVIg.
Is a 10-point composite autonomic scoring scale of autonomic function. This scale allots 4 points for adrenergic and 3 points each for sudomotor and cardiovagal failure. Subjects with a score of 3 or less on have a mild autonomic failure, 4-6 have moderate autonomic failure and those with scores of 7 to 10 have severe failure. The minimum score possible is 3 and maximum is 10.
Measured: Baseline, 6 weeks
EuroQol [EQ-5D] Questionnaire.
To determine the change in quality of life (measured by the EuroQol [EQ-5D]) measured at baseline and 6 weeks in individuals receiving IVIg. We have reported the subscale (EQ-VAS). The minimum score is 0 and maximum score is 100. (0) corresponds to " the worst health you can imagine", and the highest rate (100) corresponds to "the best health you can imagine".
Measured: Baseline, 6 weeks
Orthostatic Hypotension Symptom Assessment Questionnaire
To determine the change in orthostatic Hypotension symptom (measured by the orthostatic hypotension symptom assessment questionnaire) measured at baseline and 6 weeks in individuals receiving IVIG. This is a 60 point orthostatic hypotenstion symptom assessment questionnaire. The minimum score possible is 0 and maximum is 60.
Higher values represent worse outcome. We are reporting the total score.
Measured: Baseline, 6 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2012Sep 2015

First posted31 Jan 2012 (estimated)
Study startFeb 2012
Primary completionMay 2014
Study completionSep 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (29)Papers the sponsor has linked to this study.
Other trials for Autoimmune Autonomic Ganglionopathy (AAG)Studies of the same condition, open and under way.
More trials run by Beth Israel Deaconess Medical CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2/3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 6 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01522235
Sponsor's protocol ID: 2011P000397
Other IDs: 1U54NS065736
Status last verified: Jun 2017
First submitted: 25 Jan 2012
Last updated: 2 Jul 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes: The investigators will adhere to the NIH Grant Policy on Sharing of Unique Research Resources including the Principles and Guidelines for Recipients of NIH Research Grants and Contracts on Obtaining and Disseminating Biomedical Research Resources.

Publications

Vernino S, Sandroni P, Singer W, Low PA. Invited Article: Autonomic ganglia: target and novel therapeutic tool. Neurology. 2008 May 13;70(20):1926-32. doi: 10.1212/01.wnl.0000312280.44805.5d.
PubMed 18474849
Vernino S, Low PA, Fealey RD, Stewart JD, Farrugia G, Lennon VA. Autoantibodies to ganglionic acetylcholine receptors in autoimmune autonomic neuropathies. N Engl J Med. 2000 Sep 21;343(12):847-55. doi: 10.1056/NEJM200009213431204.
PubMed 10995864
Gibbons CH, Freeman R. Antibody titers predict clinical features of autoimmune autonomic ganglionopathy. Auton Neurosci. 2009 Mar 12;146(1-2):8-12. doi: 10.1016/j.autneu.2008.11.013. Epub 2009 Jan 13.
PubMed 19144572
Klein CM, Vernino S, Lennon VA, Sandroni P, Fealey RD, Benrud-Larson L, Sletten D, Low PA. The spectrum of autoimmune autonomic neuropathies. Ann Neurol. 2003 Jun;53(6):752-8. doi: 10.1002/ana.10556.
PubMed 12783421
Gibbons CH, Vernino SA, Kaufmann H, Freeman R. L-DOPS therapy for refractory orthostatic hypotension in autoimmune autonomic neuropathy. Neurology. 2005 Oct 11;65(7):1104-6. doi: 10.1212/01.wnl.0000178980.83477.14.
PubMed 16217067
Gibbons CH, Vernino SA, Freeman R. Combined immunomodulatory therapy in autoimmune autonomic ganglionopathy. Arch Neurol. 2008 Feb;65(2):213-7. doi: 10.1001/archneurol.2007.60.
PubMed 18268189
Iodice V, Kimpinski K, Vernino S, Sandroni P, Fealey RD, Low PA. Efficacy of immunotherapy in seropositive and seronegative putative autoimmune autonomic ganglionopathy. Neurology. 2009 Jun 9;72(23):2002-8. doi: 10.1212/WNL.0b013e3181a92b52.
PubMed 19506222
Modoni A, Mirabella M, Madia F, Sanna T, Lanza G, Tonali PA, Silvestri G. Chronic autoimmune autonomic neuropathy responsive to immunosuppressive therapy. Neurology. 2007 Jan 9;68(2):161-2. doi: 10.1212/01.wnl.0000251194.82212.75. No abstract available.
PubMed 17210903
Young RR, Asbury AK, Adams RD, Corbett JL. Pure pan-dysautonomia with recovery. Trans Am Neurol Assoc. 1969;94:355-7. No abstract available.
PubMed 5374487
Vernino S, Ermilov LG, Sha L, Szurszewski JH, Low PA, Lennon VA. Passive transfer of autoimmune autonomic neuropathy to mice. J Neurosci. 2004 Aug 11;24(32):7037-42. doi: 10.1523/JNEUROSCI.1485-04.2004.
PubMed 15306637
Malik U, Oleksowicz L, Latov N, Cardo LJ. Intravenous gamma-globulin inhibits binding of anti-GM1 to its target antigen. Ann Neurol. 1996 Jan;39(1):136-9. doi: 10.1002/ana.410390121.
PubMed 8572660
Kazatchkine MD, Kaveri SV. Immunomodulation of autoimmune and inflammatory diseases with intravenous immune globulin. N Engl J Med. 2001 Sep 6;345(10):747-55. doi: 10.1056/NEJMra993360. No abstract available.
PubMed 11547745
Dalakas MC. Intravenous immunoglobulin in autoimmune neuromuscular diseases. JAMA. 2004 May 19;291(19):2367-75. doi: 10.1001/jama.291.19.2367.
PubMed 15150209
Samuelsson A, Towers TL, Ravetch JV. Anti-inflammatory activity of IVIG mediated through the inhibitory Fc receptor. Science. 2001 Jan 19;291(5503):484-6. doi: 10.1126/science.291.5503.484.
PubMed 11161202
Dalakas MC. Blockade of blocking antibodies in Guillain-Barre syndromes: "unblocking" the mystery of action of intravenous immunoglobulin. Ann Neurol. 2002 Jun;51(6):667-9. doi: 10.1002/ana.10259. No abstract available.
PubMed 12112069

Study at a glance

From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Double-blind, Randomized, Placebo-controlled Trial to Evaluate the Efficacy of Intravenous Immunoglobulin Therapy in Autoimmune Autonomic Ganglionopathy.
ClinicalTrials.gov ID: NCT01522235
Acronym / sponsor ID: 2011P000397
Conditions: Autoimmune Autonomic Ganglionopathy (AAG)
Keywords: Autoimmune autonomic neuropathy, Orthostatic hypotension, Dysautonomia, Autonomic failure, Peripheral autonomic neuropathy
Phase: Phase 2/3
Study type: Interventional
Recruitment status: Completed
Enrolment: 6 participants (actual)
Lead sponsor: Beth Israel Deaconess Medical CenterUniversity, hospital or other
Collaborators: Mayo Clinic, Vanderbilt University, NYU Langone Health, University of Texas Southwestern Medical Center, National Institute of Neurological Disorders and Stroke (NINDS)
Study start: Feb 2012
Primary completion: May 2014 (actual)
Study completion: Sep 2015 (actual)
First posted: 31 Jan 2012 (estimated)
Results: Posted 2 Jul 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

To address these unresolved issues, this clinical trial has the following goals:

To measure the effect of IVIG treatment on orthostatic hypotension, autonomic symptoms and quality of life scores in patient participants with AAG.
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.

All the participants will then move to a single blinded second observation period.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
IVIg group	Active comparator	Drug: Double blinded IVIg, Other: Single Blinded IVIgDouble blinded IVIg and single blinded IVIg
Placebo Group	Other	Other: Double blinded Placebo, Other: Single Blinded IVIgDouble blinded Placebo and single blinded IVIg

Who may qualify

Ages: 18 to 85 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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

Key exclusion criteria (21 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Double blinded IVIgAlso: GammagardParticipants 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.	Drug	IVIg group
Double blinded PlaceboParticipants 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.	Other	Placebo Group
Single Blinded IVIgThis 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	IVIg group, Placebo Group

Primary outcome

Change in Systolic Blood Pressure During 60° Tilt (ΔSBP)
Time frame: Baseline and 6 weeks
The primary outcome, the change in systolic blood pressure during 60 degree tilt (ΔSBP), will be assessed in all study participants at baseline and at 6 weeks.

5 secondary outcomes

Change in Systolic Blood Pressure During 60° Tilt (ΔSBP)
Time frame: 6 weeks and 12 weeks
Composite Autonomic Symptom Score [COMPASS] Questionnaire
Time frame: Baseline, 6 weeks
Composite Autonomic Severity Score (CASS) Questionnaire.
Time frame: Baseline, 6 weeks
EuroQol [EQ-5D] Questionnaire.
Time frame: Baseline, 6 weeks
Orthostatic Hypotension Symptom Assessment Questionnaire
Time frame: Baseline, 6 weeks

Results and safety

Results posted to the registry on 2 Jul 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
IVIG Group	3	2
Placebo Group	3	2

Primary outcome: Change in Systolic Blood Pressure During 60° Tilt (ΔSBP)

Time frame: Baseline and 6 weeks. Mean (Standard Deviation). Unit: mmHg

Measure	IVIg Group n = 2	Placebo Group n = 3
Value	42.5 (54.4)	-12.3 (38.0)

5 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
IVIg Group	0 of 3 (0%)	1 of 2 (50%)	0 of 3
Placebo Group	0 of 3 (0%)	3 of 3 (100%)	0 of 3

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 18474849Vernino S, Sandroni P, Singer W, Low PA. Invited Article: Autonomic ganglia: target and novel therapeutic tool. Neurology. 2008 May 13;70(20):1926-32. doi: 10.1212/01.wnl.0000312280.44805.5d.
Background: PubMed 10995864Vernino S, Low PA, Fealey RD, Stewart JD, Farrugia G, Lennon VA. Autoantibodies to ganglionic acetylcholine receptors in autoimmune autonomic neuropathies. N Engl J Med. 2000 Sep 21;343(12):847-55. doi: 10.1056/NEJM200009213431204.
Background: PubMed 19144572Gibbons CH, Freeman R. Antibody titers predict clinical features of autoimmune autonomic ganglionopathy. Auton Neurosci. 2009 Mar 12;146(1-2):8-12. doi: 10.1016/j.autneu.2008.11.013. Epub 2009 Jan 13.
Background: PubMed 12783421Klein CM, Vernino S, Lennon VA, Sandroni P, Fealey RD, Benrud-Larson L, Sletten D, Low PA. The spectrum of autoimmune autonomic neuropathies. Ann Neurol. 2003 Jun;53(6):752-8. doi: 10.1002/ana.10556.
Background: PubMed 16217067Gibbons CH, Vernino SA, Kaufmann H, Freeman R. L-DOPS therapy for refractory orthostatic hypotension in autoimmune autonomic neuropathy. Neurology. 2005 Oct 11;65(7):1104-6. doi: 10.1212/01.wnl.0000178980.83477.14.
Background: PubMed 18268189Gibbons CH, Vernino SA, Freeman R. Combined immunomodulatory therapy in autoimmune autonomic ganglionopathy. Arch Neurol. 2008 Feb;65(2):213-7. doi: 10.1001/archneurol.2007.60.
Background: PubMed 19506222Iodice V, Kimpinski K, Vernino S, Sandroni P, Fealey RD, Low PA. Efficacy of immunotherapy in seropositive and seronegative putative autoimmune autonomic ganglionopathy. Neurology. 2009 Jun 9;72(23):2002-8. doi: 10.1212/WNL.0b013e3181a92b52.
Background: PubMed 17210903Modoni A, Mirabella M, Madia F, Sanna T, Lanza G, Tonali PA, Silvestri G. Chronic autoimmune autonomic neuropathy responsive to immunosuppressive therapy. Neurology. 2007 Jan 9;68(2):161-2. doi: 10.1212/01.wnl.0000251194.82212.75. No abstract available.
Background: PubMed 5374487Young RR, Asbury AK, Adams RD, Corbett JL. Pure pan-dysautonomia with recovery. Trans Am Neurol Assoc. 1969;94:355-7. No abstract available.
Background: PubMed 15306637Vernino S, Ermilov LG, Sha L, Szurszewski JH, Low PA, Lennon VA. Passive transfer of autoimmune autonomic neuropathy to mice. J Neurosci. 2004 Aug 11;24(32):7037-42. doi: 10.1523/JNEUROSCI.1485-04.2004.
Background: PubMed 8572660Malik U, Oleksowicz L, Latov N, Cardo LJ. Intravenous gamma-globulin inhibits binding of anti-GM1 to its target antigen. Ann Neurol. 1996 Jan;39(1):136-9. doi: 10.1002/ana.410390121.
Background: PubMed 11547745Kazatchkine MD, Kaveri SV. Immunomodulation of autoimmune and inflammatory diseases with intravenous immune globulin. N Engl J Med. 2001 Sep 6;345(10):747-55. doi: 10.1056/NEJMra993360. No abstract available.
Individual participant dataSharing planned: Yes. The investigators will adhere to the NIH Grant Policy on Sharing of Unique Research Resources including the Principles and Guidelines for Recipients of NIH Research Grants and Contracts on Obtaining and Disseminating Biomedical Research Resources.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Roy Freeman, MD principal investigator

Beth Israel Deaconess Medical Center

6 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Systolic Blood Pressure During 60° Tilt (ΔSBP) (time frame: Baseline and 6 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01522235, which also lists 29 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017.