Trial Outcomes & Findings for Evaluating the Effectiveness of Intravenous Immunoglobulin Therapy in Autoimmune Autonomic Ganglionopathy (NCT NCT01522235)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

6 participants

Primary outcome timeframe

Baseline and 6 weeks

Results posted on

2017-07-02

Participant Flow

Participant milestones

Participant milestones
Measure	IVIG Group IVIg 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.	Placebo Group Placebo 2 treatments of placebo and 2 treatments of IVIg: 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.
Overall Study STARTED	3	3
Overall Study Randomized	2	3
Overall Study COMPLETED	2	2
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	IVIG Group IVIg 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.	Placebo Group Placebo 2 treatments of placebo and 2 treatments of IVIg: 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.
Overall Study Physician Decision	1	1

Baseline Characteristics

Evaluating the Effectiveness of Intravenous Immunoglobulin Therapy in Autoimmune Autonomic Ganglionopathy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group A n=3 Participants IVIg 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. They 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.	Group B n=3 Participants Placebo 2 treatments of placebo and 2 treatments of IVIg: 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. They 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.	Total n=6 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	IVIg Group n=2 Participants IVIg 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. They 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.	Placebo Group n=3 Participants Placebo 2 treatments of placebo and 2 treatments of IVIG: 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. They 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)	42.5 mmHg Standard Deviation 54.4	-12.3 mmHg Standard Deviation 38.0

SECONDARY outcome

Timeframe: 6 weeks and 12 weeks

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).

Outcome measures

Outcome measures
Measure	IVIg Group n=2 Participants IVIg 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. They 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.	Placebo Group n=3 Participants Placebo 2 treatments of placebo and 2 treatments of IVIG: 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. They 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)	-26 mmHg Standard Deviation 43.8	-7.6 mmHg Standard Deviation 7.09

SECONDARY outcome

Timeframe: Baseline, 6 weeks

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.

Outcome measures

Outcome measures
Measure	IVIg Group n=2 Participants IVIg 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. They 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.	Placebo Group n=3 Participants Placebo 2 treatments of placebo and 2 treatments of IVIG: 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. They 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.
Composite Autonomic Symptom Score [COMPASS] Questionnaire	-5 units Standard Deviation 2.8	-0.33 units Standard Deviation 5.13

SECONDARY outcome

Timeframe: Baseline, 6 weeks

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.

Outcome measures

Outcome measures
Measure	IVIg Group n=2 Participants IVIg 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. They 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.	Placebo Group n=3 Participants Placebo 2 treatments of placebo and 2 treatments of IVIG: 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. They 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.
Composite Autonomic Severity Score (CASS) Questionnaire.	0.5 units Standard Deviation 0.7	0 units Standard Deviation 0

SECONDARY outcome

Timeframe: Baseline, 6 weeks

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".

Outcome measures

Outcome measures
Measure	IVIg Group n=2 Participants IVIg 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. They 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.	Placebo Group n=3 Participants Placebo 2 treatments of placebo and 2 treatments of IVIG: 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. They 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.
EuroQol [EQ-5D] Questionnaire.	15 units Standard Deviation 21.2	9.3 units Standard Deviation 22.8

SECONDARY outcome

Timeframe: Baseline, 6 weeks

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.

Outcome measures

Outcome measures
Measure	IVIg Group n=2 Participants IVIg 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. They 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.	Placebo Group n=3 Participants Placebo 2 treatments of placebo and 2 treatments of IVIG: 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. They 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.
Orthostatic Hypotension Symptom Assessment Questionnaire	-9 units Standard Deviation 2.8	12 units Standard Deviation 9.5

Adverse Events

IVIg Group

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Placebo Group

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	IVIg Group n=2 participants at risk；n=3 participants at risk IVIg 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. They 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.	Placebo Group n=3 participants at risk Placebo 2 treatments of placebo and 2 treatments of IVIg: 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. They 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.
Musculoskeletal and connective tissue disorders Arthritis	50.0% 1/2 • Number of events 1	0.00% 0/3
Gastrointestinal disorders Diarrhea	0.00% 0/2	33.3% 1/3 • Number of events 1
Musculoskeletal and connective tissue disorders pain	0.00% 0/2	33.3% 1/3 • Number of events 1
Gastrointestinal disorders nausea	0.00% 0/2	33.3% 1/3 • Number of events 1
Skin and subcutaneous tissue disorders Rash	0.00% 0/2	33.3% 1/3 • Number of events 1

Additional Information

Dr. Roy Freeman

Beth Israel Deaconess Medical Center

Phone: 6176328454

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place