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Multiple System Atrophy (MSA) is a progressive sporadic neurodegenerative disorder leading to widespread loss of brain cells that results in parkinsonian, cerebellar and autonomic dysfunction. The cause of the MSA remains unclear. Available treatment is symptomatic only and does not alter the course of disease.
Although the cause of MSA remains unclear, there is evidence of presence of common neuroinflammatory mechanisms in the MSA brains including activation of microglia and production of toxic cytokines. This research protocol is based on hypothesis that the MSA progression can be altered by blocking the neuroinflammatory activity.
This protocol includes administration of intravenous immunoglobulin (IVIg). IVIg contains antibodies derived from human plasma which can block the inflammatory responses in the brain that can lead to loss of brain cells.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | Interventions included monthly infusions of intravenous immunoglobulin. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| intravenous immunoglobulin (IVIg) | Drug | The intravenous immunoglobulin (brand Privigen) will be infused intravenously, monthly, 6 times, for 6 months the dose will be 0.4 gram/kg for each infusion. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Adverse Events up to Six Months Post-treatment | The primary outcome measure was to evaluate the safety and tolerability of the IVIG infusions in patients with multiple system atrophy. The primary endpoint was defined as the frequency of adverse events (AE). AEs including their severity and relationship to the IVIG were assessed throughout the study and at least 60 days after the last infusion. The AEs were considered to be related to the IVIG infusion (infusional AE) if they occurred during an infusion or within 72 hours afterwards. Non-infusional AEs were further classified as possible related to IVIG or likely not related to IVIG. Serious AEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization. Any AE was defined as occurrence of any symptom regardless of intensity grade. | Monthly, up to 8 months (including the screening visit and the final visit) |
| Measure | Description | Time Frame |
|---|---|---|
| Preliminary Efficacy of IVIg for Treatment of MSA. | The secondary outcome measure was to evaluate the preliminary efficacy of IVIG for the treatment of MSA. The primary efficacy endpoint was change of the Unified MSA Rating Scale (UMSARS-I and UMSAR-II) compared to baseline. UMSARS-I and UMSARS-II are validated semiquantitative rating scales for evaluation of severity of MSA. UMSARS-I comprises a historical review of disease-related impairments and UMSARS-II comprises motor examination. UMSARS-I has 12 questions, each with assigned score 0-4, where 0 is normal and > are abnormal responses. Total range of UMSARS-I is 0 to 48. UMSARS-II has 12 items rated by an examiner, each with assigned score 0-4, where 0 is normal and > are abnormal responses. Total range of UMSARS-II is 0 to 56. The scores of UMSARS-I and UMSARS-II at baseline (month 1) was compared with the scores obtained at the final visit (month 8) which was 8 months apart. The interventions occured at months 2-7, total six times. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Peter Novak, MD, PhD | University of Massachusetts, Worcester | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Massachusetts Medical School | Worcester | Massachusetts | 01655 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23116538 | Result | Novak P, Williams A, Ravin P, Zurkiya O, Abduljalil A, Novak V. Treatment of multiple system atrophy using intravenous immunoglobulin. BMC Neurol. 2012 Nov 1;12:131. doi: 10.1186/1471-2377-12-131. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Open Label Interventional Arm | intravenous immunoglobulin (IVIg): The IVIg will be infused intravenously, monthly, 6 times, the dose will be 0.4 gram/kg for each infusion. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Open Label Interventional Arm | intravenous immunoglobulin (IVIg): The IVIg will be infused intravenously, monthly, 6 times, the dose will be 0.4 gram/kg for each infusion. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Adverse Events up to Six Months Post-treatment | The primary outcome measure was to evaluate the safety and tolerability of the IVIG infusions in patients with multiple system atrophy. The primary endpoint was defined as the frequency of adverse events (AE). AEs including their severity and relationship to the IVIG were assessed throughout the study and at least 60 days after the last infusion. The AEs were considered to be related to the IVIG infusion (infusional AE) if they occurred during an infusion or within 72 hours afterwards. Non-infusional AEs were further classified as possible related to IVIG or likely not related to IVIG. Serious AEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization. Any AE was defined as occurrence of any symptom regardless of intensity grade. | Two participants dropped out from the study. | Posted | Number | Adverse events | Monthly, up to 8 months (including the screening visit and the final visit) |
|
1 year
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Open Label Interventional Arm | intravenous immunoglobulin (IVIg): The IVIg will be infused intravenously, monthly, 6 times, the dose will be 0.4 gram/kg for each infusion. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| elevated blood pressure | Vascular disorders | Systematic Assessment | transient, responding to adjusting the infusion rate |
The main study limitation is its small size and open label character.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr.Peter Novak | University of Massachusetts Medical School | 508-334-4973 | novakp@ummhc.org |
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| ID | Term |
|---|---|
| D019578 | Multiple System Atrophy |
| C563206 | Thyroid Dyshormonogenesis 2A |
| ID | Term |
|---|---|
| D054969 | Primary Dysautonomias |
| D001342 | Autonomic Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D001480 | Basal Ganglia Diseases |
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| ID | Term |
|---|---|
| D016756 | Immunoglobulins, Intravenous |
| ID | Term |
|---|---|
| D007074 | Immunoglobulin G |
| D007132 | Immunoglobulin Isotypes |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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|
| Monthly, up to 8 months (including the screening visit and the final visit) |
| years |
|
| Age, Categorical | Count of Participants | Participants |
|
| Gender | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Open Label Interventional Arm |
intravenous immunoglobulin (IVIg): The IVIg will be infused intravenously, monthly, 6 times, the dose will be 0.4 gram/kg for each infusion. |
|
|
| Secondary | Preliminary Efficacy of IVIg for Treatment of MSA. | The secondary outcome measure was to evaluate the preliminary efficacy of IVIG for the treatment of MSA. The primary efficacy endpoint was change of the Unified MSA Rating Scale (UMSARS-I and UMSAR-II) compared to baseline. UMSARS-I and UMSARS-II are validated semiquantitative rating scales for evaluation of severity of MSA. UMSARS-I comprises a historical review of disease-related impairments and UMSARS-II comprises motor examination. UMSARS-I has 12 questions, each with assigned score 0-4, where 0 is normal and > are abnormal responses. Total range of UMSARS-I is 0 to 48. UMSARS-II has 12 items rated by an examiner, each with assigned score 0-4, where 0 is normal and > are abnormal responses. Total range of UMSARS-II is 0 to 56. The scores of UMSARS-I and UMSARS-II at baseline (month 1) was compared with the scores obtained at the final visit (month 8) which was 8 months apart. The interventions occured at months 2-7, total six times. | Posted | Mean | Standard Deviation | units on a scale | Monthly, up to 8 months (including the screening visit and the final visit) |
|
|
|
|
| 0 |
| 9 |
| 9 |
| 9 |
|
| urinary tract infection | Infections and infestations | Systematic Assessment | treated with antibiotics |
|
| Accidental injury | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | nose fracture |
|
| pruritic skin rash | Skin and subcutaneous tissue disorders | Systematic Assessment | 2 subjects withdrew from the study. |
|
| increased temperature or skin flushing | Skin and subcutaneous tissue disorders | Systematic Assessment | treated with Diphenhydramine, Acetaminophen, and slowing the infusion rate |
|
| restless leg syndrome | Musculoskeletal and connective tissue disorders | Systematic Assessment | treated with iron supplements |
|
| decreased GFR | Renal and urinary disorders | Systematic Assessment | resolved |
|
| ankle edema | Vascular disorders | Systematic Assessment | treated with diuretics |
|
| elevated BUN | Renal and urinary disorders | Systematic Assessment | resolved |
|
| worsening of allergies | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| nodular lung abnormality | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | later determined to be a tangle of vein most likely inborn |
|
| low potassium | Endocrine disorders | Systematic Assessment | treated with potassium supplements |
|
| viral infection of gastrointenstinal tract | Gastrointestinal disorders | Systematic Assessment | resolved |
|
| elevated PSA | Reproductive system and breast disorders | Systematic Assessment | resolved |
|
| wrist strain | Musculoskeletal and connective tissue disorders | Systematic Assessment | resolved |
|
| worsening of sleep apnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | treated with continuous positive airway pressure (CPAP) |
|
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| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| Title | Measurements |
|---|---|
|
| UMSARS-II, final visit |
|
The P-Value was obtained by comparing the UMSARS-II scores at final visit and at baseline. |
| No |
| Superiority or Other |