A Phase 2/3 interventional study of Double blinded IVIg and Double blinded Placebo in Autoimmune Autonomic Ganglionopathy (AAG), sponsored by Beth Israel Deaconess Medical Center. Completed at 6 sites in United States. Open to participants aged 18 Years to 85 Years. Per ClinicalTrials.gov, last updated 2017-07-02.
Sponsored by Beth Israel Deaconess Medical Center · Phase 2/3, Interventional, and Treatment
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).
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:
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).
Beth Israel Deaconess Medical Center is the lead sponsor of 560 studies on the registry; 80 are open to participants now.
Of its 75 completed or terminated interventional studies of FDA-regulated products, 61 (81%) have results posted.
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Exclusion Criteria:
Double blinded IVIg and single blinded IVIg
Drug: Double blinded IVIg · Other: Single Blinded IVIg
Double blinded Placebo and single blinded IVIg
Other: Double blinded Placebo · Other: Single Blinded IVIg
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.
Also known as: Gammagard
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.
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.
Time frame: Baseline and 6 weeks
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).
Time frame: 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.
Time frame: 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.
Time frame: 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".
Time frame: 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.
Time frame: Baseline, 6 weeks
| Milestone | IVIG Group | Placebo Group |
|---|---|---|
| Started | 3 | 3 |
| Randomized | 2 | 3 |
| Completed | 2 | 2 |
| Not completed | 1 | 1 |
| Withdrew: Physician decision | 1 | 1 |
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.
| mmHg | IVIg Group | Placebo Group |
|---|---|---|
| Change in Systolic Blood Pressure During 60° Tilt (ΔSBP) | 42.5 ± 54.4 | -12.3 ± 38.0 |
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).
| mmHg | IVIG Group | Placebo Group |
|---|---|---|
| Change in Systolic Blood Pressure During 60° Tilt (ΔSBP) | -26 ± 43.8 | -7.6 ± 7.09 |
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.
| units | IVIg Group | Placebo Group |
|---|---|---|
| Composite Autonomic Symptom Score [COMPASS] Questionnaire | -5 ± 2.8 | -0.33 ± 5.13 |
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.
| units | IVIg Group | Placebo Group |
|---|---|---|
| Composite Autonomic Severity Score (CASS) Questionnaire. | 0.5 ± 0.7 | 0 ± 0 |
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".
| units | IVIg Group | Placebo Group |
|---|---|---|
| EuroQol [EQ-5D] Questionnaire. | 15 ± 21.2 | 9.3 ± 22.8 |
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.
| units | Group A | Group B |
|---|---|---|
| Orthostatic Hypotension Symptom Assessment Questionnaire | -9 ± 2.8 | 12 ± 9.5 |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| IVIg Group | 0/3 (0%) | 0/3 (0%) | 1/2 (50%) |
| Placebo Group | 0/3 (0%) | 0/3 (0%) | 3/3 (100%) |
| Event | IVIg Group | Placebo Group |
|---|---|---|
| ArthritisMusculoskeletal and connective tissue disorders | 1/2 | 0/3 |
| DiarrheaGastrointestinal disorders | 0/2 | 1/3 |
| painMusculoskeletal and connective tissue disorders | 0/2 | 1/3 |
| nauseaGastrointestinal disorders | 0/2 | 1/3 |
| RashSkin and subcutaneous tissue disorders | 0/2 | 1/3 |
| RashSkin and subcutaneous tissue disorders | 0/2 | 1/3 |
| Age, Categorical(Participants) | Group A | Group B | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 3 | 3 | 6 |
| >=65 years | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | Group A | Group B | Total |
|---|---|---|---|
| Female | 1 | 3 | 4 |
| Male | 2 | 0 | 2 |
Plan to share: 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.
This study is completed, as verified in Jun 2017. You cannot join it, but the record below documents what was studied.
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Beth Israel Deaconess Medical Center