Multiple System Atrophy
Conditions
Keywords
multiple system atrophy, MSA,, intravenous immunoglobulin, IVIg
Brief summary
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.
Interventions
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.
Sponsors
University of Massachusetts, Worcester
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female older than 17 years. 2. Clinical diagnosis of probable multiple system atrophy 3. Provide written informed consent to participate in the study 4. Understand that they may withdraw their consent at any time
Exclusion criteria
1. Women who are pregnant or lactating 2. In the investigator's opinion, have any other significant systemic, hepatic, cardiac or renal illness. 3. In the investigator's opinion, the subjects are significantly dehydrated, as determined by clinical evaluation including measurement of skin turgor, blood urea nitrogen and creatinine values.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events up to Six Months Post-treatment | Monthly, up to 8 months (including the screening visit and the final visit) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Preliminary Efficacy of IVIg for Treatment of MSA. | Monthly, up to 8 months (including the screening visit and the final visit) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
Baseline characteristics
| Characteristic | Open Label Interventional Arm |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age, Continuous | 59 years |
| Gender Female | 3 Participants |
| Gender Male | 6 Participants |
| Region of Enrollment United States | 9 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 9 |
| serious Total, serious adverse events | 0 / 9 |
Outcome results
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.
Time frame: Monthly, up to 8 months (including the screening visit and the final visit)
Population: Two participants dropped out from the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Open Label Interventional Arm | Number of Adverse Events up to Six Months Post-treatment | All Adverse Events | 43 Adverse events |
| Open Label Interventional Arm | Number of Adverse Events up to Six Months Post-treatment | Serious Adverse Events | 0 Adverse events |
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.
Time frame: Monthly, up to 8 months (including the screening visit and the final visit)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Open Label Interventional Arm | Preliminary Efficacy of IVIg for Treatment of MSA. | UMSARS-I, baseline | 23.8 units on a scale | Standard Deviation 6 |
| Open Label Interventional Arm | Preliminary Efficacy of IVIg for Treatment of MSA. | UMSARS-II,baseline | 26.1 units on a scale | Standard Deviation 7.4 |
| Open Label Interventional Arm | Preliminary Efficacy of IVIg for Treatment of MSA. | UMSARS-I, final visit | 19 units on a scale | Standard Deviation 5.9 |
| Open Label Interventional Arm | Preliminary Efficacy of IVIg for Treatment of MSA. | UMSARS-II, final visit | 23.3 units on a scale | Standard Deviation 7.2 |
p-value: 0.0128ANOVA
p-value: 0.025ANOVA