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A Futility Trial of Sirolimus in Multiple System Atrophy

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ClinicalTrials.gov Identifier: NCT03589976
Recruitment Status : Terminated (Interim analysis showed early evidence of futility of sirolimus. Trial stopped per DSMB recommendation.)
First Posted : July 18, 2018
Results First Posted : December 7, 2021
Last Update Posted : December 7, 2021
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
NYU Langone Health

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Single Group Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Multiple System Atrophy
Interventions Drug: Sirolimus 2 MG
Other: Placebo
Enrollment 47
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Sirolimus Placebo
Hide Arm/Group Description

2 mg/day (one 2-mg tablet/day). The dose of sirolimus will be adjusted throughout the trial based on sirolimus plasma levels and the presence of drug-related adverse events. The maximum dose of sirolimus will be6 mg/day (three 2-mg tablets/day).

Sirolimus 2 MG: Dose will be adjusted throughout this trial based on sirolimus plasma levels and the presence of drug-related adverse events. The maximum dose will be 6mg/day.

Patients receiving placebo will undergo analog sham level measurements and the number of tablets will be also adjusted to maintain the blinding of the trial.

Placebo: Patients receiving placebo will undergo analog sham level measurements and the number of tablets will be also adjusted to maintain the blinding of the trial.

Period Title: Overall Study
Started 35 12
Completed 16 6
Not Completed 19 6
Reason Not Completed
Death             5             1
Adverse Event             5             1
Withdrawal by Subject             4             1
Lost to Follow-up             1             0
Other             4             3
Arm/Group Title Sirolimus Placebo Total
Hide Arm/Group Description

2 mg/day (one 2-mg tablet/day). The dose of sirolimus will be adjusted throughout the trial based on sirolimus plasma levels and the presence of drug-related adverse events. The maximum dose of sirolimus will be6 mg/day (three 2-mg tablets/day).

Sirolimus 2 MG: Dose will be adjusted throughout this trial based on sirolimus plasma levels and the presence of drug-related adverse events. The maximum dose will be 6mg/day.

Patients receiving placebo will undergo analog sham level measurements and the number of tablets will be also adjusted to maintain the blinding of the trial.

Placebo: Patients receiving placebo will undergo analog sham level measurements and the number of tablets will be also adjusted to maintain the blinding of the trial.

Total of all reporting groups
Overall Number of Baseline Participants 35 12 47
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 35 participants 12 participants 47 participants
59
(56 to 63)
58
(56 to 63)
58
(56 to 63)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 35 participants 12 participants 47 participants
Female
14
  40.0%
6
  50.0%
20
  42.6%
Male
21
  60.0%
6
  50.0%
27
  57.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 35 participants 12 participants 47 participants
Hispanic or Latino
2
   5.7%
1
   8.3%
3
   6.4%
Not Hispanic or Latino
33
  94.3%
11
  91.7%
44
  93.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 35 participants 12 participants 47 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
3
   8.6%
0
   0.0%
3
   6.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
   5.7%
0
   0.0%
2
   4.3%
White
30
  85.7%
12
 100.0%
42
  89.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 35 participants 12 participants 47 participants
35 12 47
1.Primary Outcome
Title Change From Baseline to 48 Weeks in United Multiple System Atrophy Rating Score (UMSARS) Total Score
Hide Description

UMSARS is a validated, disease-specific scale representing the diverse signs and symptoms in MSA.

USMARS has an Activities of Daily Living score (UMSARS-1, 12 questions) that evaluates motor including autonomic activities and the Motor Examination score (UMSARS-2, 14 questions). UMSARS-3 measures supine/standing BP and UMSARS-4 is a disability scale.

The total range of score is 1-109; Higher scores on the UMSARS scales mean poorer health.

Time Frame Baseline, 48 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sirolimus Placebo
Hide Arm/Group Description:

2 mg/day (one 2-mg tablet/day). The dose of sirolimus will be adjusted throughout the trial based on sirolimus plasma levels and the presence of drug-related adverse events. The maximum dose of sirolimus will be6 mg/day (three 2-mg tablets/day).

Sirolimus 2 MG: Dose will be adjusted throughout this trial based on sirolimus plasma levels and the presence of drug-related adverse events. The maximum dose will be 6mg/day.

Patients receiving placebo will undergo analog sham level measurements and the number of tablets will be also adjusted to maintain the blinding of the trial.

Placebo: Patients receiving placebo will undergo analog sham level measurements and the number of tablets will be also adjusted to maintain the blinding of the trial.

Overall Number of Participants Analyzed 25 9
Mean (Standard Deviation)
Unit of Measure: score on a scale
13.92  (8.32) 11.3  (8)
2.Secondary Outcome
Title Change From Baseline to 48 Weeks in UMSARS-1
Hide Description

The Activities of Daily Living score (UMSARS-1, 12 questions) evaluates impact of symptoms, including autonomic, on activities of daily living.

12 functional situations are rated between 0-4. The total range of score is 0-48; the higher the score, the more problems conducting activities of daily living.

Time Frame Baseline, 48 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sirolimus Placebo
Hide Arm/Group Description:

2 mg/day (one 2-mg tablet/day). The dose of sirolimus will be adjusted throughout the trial based on sirolimus plasma levels and the presence of drug-related adverse events. The maximum dose of sirolimus will be6 mg/day (three 2-mg tablets/day).

Sirolimus 2 MG: Dose will be adjusted throughout this trial based on sirolimus plasma levels and the presence of drug-related adverse events. The maximum dose will be 6mg/day.

Patients receiving placebo will undergo analog sham level measurements and the number of tablets will be also adjusted to maintain the blinding of the trial.

Placebo: Patients receiving placebo will undergo analog sham level measurements and the number of tablets will be also adjusted to maintain the blinding of the trial.

Overall Number of Participants Analyzed 25 9
Mean (Standard Deviation)
Unit of Measure: score on a scale
5.65  (5.91) 5.33  (3.81)
Time Frame month 12 after initiation of study drug) (+ 15 days)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Sirolimus Placebo
Hide Arm/Group Description

2 mg/day (one 2-mg tablet/day). The dose of sirolimus will be adjusted throughout the trial based on sirolimus plasma levels and the presence of drug-related adverse events. The maximum dose of sirolimus will be6 mg/day (three 2-mg tablets/day).

Sirolimus 2 MG: Dose will be adjusted throughout this trial based on sirolimus plasma levels and the presence of drug-related adverse events. The maximum dose will be 6mg/day.

Patients receiving placebo will undergo analog sham level measurements and the number of tablets will be also adjusted to maintain the blinding of the trial.

Placebo: Patients receiving placebo will undergo analog sham level measurements and the number of tablets will be also adjusted to maintain the blinding of the trial.

All-Cause Mortality
Sirolimus Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   5/35 (14.29%)   1/12 (8.33%) 
Hide Serious Adverse Events
Sirolimus Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   9/35 (25.71%)   2/12 (16.67%) 
General disorders     
Death *  5/35 (14.29%)  1/12 (8.33%) 
Other *  4/35 (11.43%)  1/12 (8.33%) 
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Sirolimus Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   31/35 (88.57%)   9/12 (75.00%) 
Gastrointestinal disorders     
Diarrhea *  16/35 (45.71%)  2/12 (16.67%) 
Nausea *  3/35 (8.57%)  1/12 (8.33%) 
General disorders     
Fatigue *  1/35 (2.86%)  7/12 (58.33%) 
Other *  25/35 (71.43%)  4/12 (33.33%) 
Infections and infestations     
Infections * [1]  21/35 (60.00%)  4/12 (33.33%) 
Nervous system disorders     
Fall *  6/35 (17.14%)  4/12 (33.33%) 
Worsening of Movement Disorder *  4/35 (11.43%)  1/12 (8.33%) 
Skin and subcutaneous tissue disorders     
Aphthae, gingivitis, and oral herpes-like vesicles *  15/35 (42.86%)  2/12 (16.67%) 
Acne, Petechiae, Rash *  13/35 (37.14%)  2/12 (16.67%) 
Vascular disorders     
Edema in Lower Limbs *  17/35 (48.57%)  1/12 (8.33%) 
*
Indicates events were collected by non-systematic assessment
[1]
Urinary tract infection, upper respiratory infection, skin infection, sinus infection
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Jose-Alberto Palma, MD, PhD
Organization: NYU Langone Health
Phone: 212-263-7225
EMail: JoseAlberto.PalmaCarazo@nyulangone.org
Layout table for additonal information
Responsible Party: NYU Langone Health
ClinicalTrials.gov Identifier: NCT03589976    
Other Study ID Numbers: 17-01392
First Submitted: July 5, 2018
First Posted: July 18, 2018
Results First Submitted: November 8, 2021
Results First Posted: December 7, 2021
Last Update Posted: December 7, 2021