Trial Outcomes & Findings for Progression Rate of MSA Under EGCG Supplementation as Anti-Aggregation-Approach (NCT NCT02008721)
NCT ID: NCT02008721
Last Updated: 2024-03-12
Results Overview
To assess the efficacy of EGCG vs. Placebo to reduce the progression in the motor examination (ME) of the Unified MSA Rating Scale (UMSARS-ME) from V1 to V7. The UMSARS-ME (Unified Multiple System Atrophy Rating Scale, Motor examination) assesses 14 operationalised signs of multiple system atrophy. 25 Scores for all 14 items range from 0 to 4, thus total scores range from 0 to 56. Higher scores mean a worse outcome.
COMPLETED
PHASE3
92 participants
52 weeks
2024-03-12
Participant Flow
Participant milestones
| Measure |
EGCG as Putative Neuroprotective Agent
Treatment with 800 mg - 1200 mg EGCG as putative neuroprotective agent
EGCG as putative neuroprotective agent: Treatment with 800 mg - 1200 mg EGCG as putative neuroprotective agent
|
Placebo
Placebo
Placebo: Placebo
|
|---|---|---|
|
Overall Study
STARTED
|
47
|
45
|
|
Overall Study
Completion of Study Assessment
|
31
|
33
|
|
Overall Study
Completion Without Protocol Violation
|
30
|
33
|
|
Overall Study
Participation in MRI Substudy
|
17
|
15
|
|
Overall Study
Completion of MRI Substudy
|
11
|
8
|
|
Overall Study
COMPLETED
|
32
|
35
|
|
Overall Study
NOT COMPLETED
|
15
|
10
|
Reasons for withdrawal
| Measure |
EGCG as Putative Neuroprotective Agent
Treatment with 800 mg - 1200 mg EGCG as putative neuroprotective agent
EGCG as putative neuroprotective agent: Treatment with 800 mg - 1200 mg EGCG as putative neuroprotective agent
|
Placebo
Placebo
Placebo: Placebo
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
5
|
1
|
|
Overall Study
Death
|
4
|
2
|
|
Overall Study
Adverse Event
|
3
|
5
|
|
Overall Study
Protocol Violation
|
3
|
2
|
Baseline Characteristics
Progression Rate of MSA Under EGCG Supplementation as Anti-Aggregation-Approach
Baseline characteristics by cohort
| Measure |
EGCG as Putative Neuroprotective Agent
n=47 Participants
Treatment with 800 mg - 1200 mg EGCG as putative neuroprotective agent
EGCG as putative neuroprotective agent: Treatment with 800 mg - 1200 mg EGCG as putative neuroprotective agent
|
Placebo
n=45 Participants
Placebo
Placebo: Placebo
|
Total
n=92 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
60 years
n=5 Participants
|
64 years
n=7 Participants
|
62 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
37 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
29 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
55 Participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
47 Participants
n=5 Participants
|
45 Participants
n=7 Participants
|
92 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 52 weeksPopulation: Eligible patients were older than 30 years; met the diagnostic criteria for possible or probable parkinsonism-predominant or cerebellar-ataxia-predominant multiple system atrophy; could ambulate independently (ie, Hoehn and Yahr stages 1-3); and had to be on stable anti-Parkinson's, anti-dysautonomia, anti-dementia, and anti-depressant regimens.
To assess the efficacy of EGCG vs. Placebo to reduce the progression in the motor examination (ME) of the Unified MSA Rating Scale (UMSARS-ME) from V1 to V7. The UMSARS-ME (Unified Multiple System Atrophy Rating Scale, Motor examination) assesses 14 operationalised signs of multiple system atrophy. 25 Scores for all 14 items range from 0 to 4, thus total scores range from 0 to 56. Higher scores mean a worse outcome.
Outcome measures
| Measure |
EGCG as Putative Neuroprotective Agent
n=47 Participants
Treatment with 800 mg - 1200 mg EGCG as putative neuroprotective agent
|
Placebo
n=45 Participants
Placebo
Placebo: Placebo
|
|---|---|---|
|
Change of Score in Motor Examination (ME) of the Unified MSA Rating Scale (UMSARS-ME) From V1 to V7.
|
5.66 score on a scale
Standard Deviation 1.01
|
6.60 score on a scale
Standard Deviation 0.99
|
SECONDARY outcome
Timeframe: 4 weeksPopulation: Eligible patients were older than 30 years; met the diagnostic criteria for possible or probable parkinsonism-predominant or cerebellar-ataxia-predominant multiple system atrophy; could ambulate independently (ie, Hoehn and Yahr stages 1-3); and had to be on stable anti-Parkinson's, anti-dysautonomia, anti-dementia, and anti-depressant regimens.
To assess any effect of EGCG vs. Placebo on the evolution of the above mentioned parameters during the wash-out phase (from V6-V7) measured by the UMSARS - ME. The UMSARS-ME (Unified Multiple System Atrophy Rating Scale, Motor examination) assesses 14 operationalised signs of multiple system atrophy. 25 Scores for all 14 items range from 0 to 4, thus total scores range from 0 to 56. Higher scores mean a worse outcome.
Outcome measures
| Measure |
EGCG as Putative Neuroprotective Agent
n=47 Participants
Treatment with 800 mg - 1200 mg EGCG as putative neuroprotective agent
|
Placebo
n=45 Participants
Placebo
Placebo: Placebo
|
|---|---|---|
|
Possible Symptomatic Effects of EGCG vs. Placebo Measured by the Change in the UMSARS - ME in the Wash-out Phase (From V6-V7)
|
0.68 score on a scale
Standard Deviation 0.60
|
0.49 score on a scale
Standard Deviation 0.58
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: Eligible patients were older than 30 years; met the diagnostic criteria for possible or probable parkinsonism-predominant or cerebellar-ataxia-predominant multiple system atrophy; could ambulate independently (ie, Hoehn and Yahr stages 1-3); and had to be on stable anti-Parkinson's, anti-dysautonomia, anti-dementia, and anti-depressant regimens.
To assess the efficacy of EGCG vs. Placebo to reduce the progression from V1 to V7 in UMSARS total score The total score of the UMSARS (Unified Multiple System Atrophy Rating Scale) is a disease specific rating scale that comprises the activities of daily living subscale and the motor examination subscale. The activities of daily living subscale assesses motor symptoms and autonomic symptoms (items 1-12 of the UMSARS activities of daily living subscale) with scores from 0-4 for every item, resulting in a minimum score of 0 and a maximum score of 48. A higher score means a worse outcome. It also includes the 14 items of the UMSARS motor examination subscale with possible scores from 0-4 for every item, resulting in a score range from 0-56. The UMSARS total score hence shows a range from 0 to 104. Higher scores indicate a greater impairment.
Outcome measures
| Measure |
EGCG as Putative Neuroprotective Agent
n=47 Participants
Treatment with 800 mg - 1200 mg EGCG as putative neuroprotective agent
|
Placebo
n=45 Participants
Placebo
Placebo: Placebo
|
|---|---|---|
|
Change in the UMSARS Total Score From V1 to V7
|
10.33 score on a scale
Standard Deviation 1.73
|
10.35 score on a scale
Standard Deviation 1.71
|
SECONDARY outcome
Timeframe: 4 weeksPopulation: Eligible patients were older than 30 years; met the diagnostic criteria for possible or probable parkinsonism-predominant or cerebellar-ataxia-predominant multiple system atrophy; could ambulate independently (ie, Hoehn and Yahr stages 1-3); and had to be on stable anti-Parkinson's, anti-dysautonomia, anti-dementia, and anti-depressant regimens.
To assess any effect of EGCG vs. Placebo on the UMSARS total score during the wash-out phase (from V6 to V7) to explore possible symptomatic effects. The total score of the UMSARS (Unified Multiple System Atrophy Rating Scale) is a disease specific rating scale that comprises the activities of daily living subscale and the motor examination subscale. The activities of daily living subscale assesses motor symptoms and autonomic symptoms (items 1-12 of the UMSARS activities of daily living subscale) with scores from 0-4 for every item, resulting in a minimum score of 0 and a maximum score of 48. A higher score means a worse outcome. It also includes the 14 items of the UMSARS motor examination subscale with possible scores from 0-4 for every item, resulting in a score range from 0-56. The UMSARS total score hence shows a range from 0 to 104, a higher score indicates greater impairment.
Outcome measures
| Measure |
EGCG as Putative Neuroprotective Agent
n=47 Participants
Treatment with 800 mg - 1200 mg EGCG as putative neuroprotective agent
|
Placebo
n=45 Participants
Placebo
Placebo: Placebo
|
|---|---|---|
|
Possible Symptomatic Effects of EGCG vs. Placebo Measured by the UMSARS Total Score From V6 to V7 (During the Washout Phase)
|
0.70 score on a scale
Standard Deviation 0.91
|
-0.29 score on a scale
Standard Deviation 0.88
|
SECONDARY outcome
Timeframe: baseline to 52 weeksPopulation: 17 patients in the EGCG-group and 15 patients in the placebo group took part in the MRI substudy. A reduced number of 11 patients were analysed in the EGCG group and 8 patients in the Placebo group, as only these patients had taken part in the follow-up MRI assessments.
To assess the efficacy of EGCG vs. Placebo to reduce the progression from V1 to V7 (52 weeks) in striatal volume loss measured by MRI (3D MP-RAGE MRI volumetry, 3D FLAIR)
Outcome measures
| Measure |
EGCG as Putative Neuroprotective Agent
n=11 Participants
Treatment with 800 mg - 1200 mg EGCG as putative neuroprotective agent
|
Placebo
n=8 Participants
Placebo
Placebo: Placebo
|
|---|---|---|
|
Percentage of Striatal Volume Loss in MRI (3D MP-RAGE MRI Volumetry, 3D FLAIR) From Baseline to V7 as Effect of Treatment (Epigallocatechin Gallate vs Placebo)
|
-0.029 % of volume loss
Standard Deviation 0.027
|
-0.064 % of volume loss
Standard Deviation 0.026
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: Eligible patients were older than 30 years; met the diagnostic criteria for possible or probable parkinsonism-predominant or cerebellar-ataxia-predominant multiple system atrophy; could ambulate independently (ie, Hoehn and Yahr stages 1-3); and had to be on stable anti-Parkinson's, anti-dysautonomia, anti-dementia, and anti-depressant regimens.
Clinical safety and tolerability of EGCG measured by number of deaths in EGCG- Group vs Placebo-Group
Outcome measures
| Measure |
EGCG as Putative Neuroprotective Agent
n=47 Participants
Treatment with 800 mg - 1200 mg EGCG as putative neuroprotective agent
|
Placebo
n=45 Participants
Placebo
Placebo: Placebo
|
|---|---|---|
|
Clinical Safety and Tolerability of EGCG Measured by Death Rates
|
4 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: Eligible patients were older than 30 years; met the diagnostic criteria for possible or probable parkinsonism-predominant or cerebellar-ataxia-predominant multiple system atrophy; could ambulate independently (ie, Hoehn and Yahr stages 1-3); and had to be on stable anti-Parkinson's, anti-dysautonomia, anti-dementia, and anti-depressant regimens.
Effect of Treatment (Epigallocatechin Gallate vs Placebo) on Safety and Tolerability: Measured by Discontinuation rates because of hepatotoxicity (measured by increased aminotransferase concentrations)
Outcome measures
| Measure |
EGCG as Putative Neuroprotective Agent
n=47 Participants
Treatment with 800 mg - 1200 mg EGCG as putative neuroprotective agent
|
Placebo
n=45 Participants
Placebo
Placebo: Placebo
|
|---|---|---|
|
Effect of Treatment (Epigallocatechin Gallate vs Placebo) on Safety and Tolerability: Discontinuation Rates Because of Hepatotoxicity
|
2 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: At baseline visit (max. 4 weeks after the screening visit)Population: Eligible patients were older than 30 years; met the diagnostic criteria for possible or probable parkinsonism-predominant or cerebellar-ataxia-predominant multiple system atrophy; could ambulate independently (ie, Hoehn and Yahr stages 1-3); and had to be on stable anti-Parkinson's, anti-dysautonomia, anti-dementia, and anti-depressant regimens.
Clinical Global Impression of Severity (CGI-S) is a 7 item scale that requires the clinician to rate the severity of the patient's illness at the time of assessment. Possible ratings are: 1. Normal, not at all ill 2. Borderline mentally ill 3. Mildly ill 4. Moderately ill 5. Markedly ill 6. Severely ill 7. Among the most extremely ill patients
Outcome measures
| Measure |
EGCG as Putative Neuroprotective Agent
n=47 Participants
Treatment with 800 mg - 1200 mg EGCG as putative neuroprotective agent
|
Placebo
n=45 Participants
Placebo
Placebo: Placebo
|
|---|---|---|
|
Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 1
Severity of illness=1
|
2 participants
|
1 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 1
severity of illness =2
|
1 participants
|
0 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 1
severity of illness=3
|
8 participants
|
6 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 1
severity of illness=4
|
23 participants
|
17 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 1
severity of illness=5
|
13 participants
|
20 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 1
severity of illness=6
|
0 participants
|
1 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 1
severity of illness=7
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Visit 5 (30 weeks after Baseline Visit)Population: Eligible patients were older than 30 years; met the diagnostic criteria for possible or probable parkinsonism-predominant or cerebellar-ataxia-predominant multiple system atrophy; could ambulate independently (ie, Hoehn and Yahr stages 1-3); and had to be on stable anti-Parkinson's, anti-dysautonomia, anti-dementia, and anti-depressant regimens. In the EGCG group only 36 of 47 patients provided data at visit 5 due to SAE/drop out; likewise in the placebo group only 37 of 45 patients.
Clinical Global Impression of Severity (CGI-S) is a 7 item scale that requires the clinician to rate the severity of the patient's illness at the time of assessment. Possible ratings are: 1. Normal, not at all ill 2. Borderline mentally ill 3. Mildly ill 4. Moderately ill 5. Markedly ill 6. Severely ill 7. Among the most extremely ill patients
Outcome measures
| Measure |
EGCG as Putative Neuroprotective Agent
n=36 Participants
Treatment with 800 mg - 1200 mg EGCG as putative neuroprotective agent
|
Placebo
n=37 Participants
Placebo
Placebo: Placebo
|
|---|---|---|
|
Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 5
Illness Level =1
|
1 participants
|
0 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 5
Illness Level=2
|
1 participants
|
0 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 5
Illness Level =3
|
6 participants
|
5 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 5
Illness Level =4
|
7 participants
|
9 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 5
Illness Level =5
|
15 participants
|
17 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 5
Illness Level =6
|
6 participants
|
6 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 5
Illness Level=7
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: 48 weeks after baseline visitPopulation: Eligible patients were older than 30 years; met the diagnostic criteria for possible or probable parkinsonism-predominant or cerebellar-ataxia-predominant multiple system atrophy; could ambulate independently (ie, Hoehn and Yahr stages 1-3); and had to be on stable anti-Parkinson's, anti-dysautonomia, anti-dementia, and anti-depressant regimens. In the EGCG group only 32 of 47 patients provided data at visit 6 due to SAE/drop out; likewise in the placebo group only 35 of 45 patients.
Clinical Global Impression of Severity (CGI-S) is a 7 item scale that requires the clinician to rate the severity of the patient's illness at the time of assessment. Possible ratings are: 1. Normal, not at all ill 2. Borderline mentally ill 3. Mildly ill 4. Moderately ill 5. Markedly ill 6. Severely ill 7. Among the most extremely ill patients
Outcome measures
| Measure |
EGCG as Putative Neuroprotective Agent
n=32 Participants
Treatment with 800 mg - 1200 mg EGCG as putative neuroprotective agent
|
Placebo
n=35 Participants
Placebo
Placebo: Placebo
|
|---|---|---|
|
Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 6
severity of illness=1
|
1 participants
|
0 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 6
severity of illness=2
|
1 participants
|
0 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 6
severity of illness=3
|
6 participants
|
3 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 6
severity of illness=4
|
6 participants
|
12 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 6
severity of illness=5
|
9 participants
|
11 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 6
severity of illness=6
|
9 participants
|
9 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 6
severity of illness=7
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: 52 weeks after baseline visitPopulation: Eligible patients were older than 30 years; met the diagnostic criteria for possible or probable parkinsonism-predominant or cerebellar-ataxia-predominant multiple system atrophy; could ambulate independently (ie, Hoehn and Yahr stages 1-3); and had to be on stable anti-Parkinson's, anti-dysautonomia, anti-dementia, and anti-depressant regimens. In the EGCG group only 23 of 47 patients provided data at visit 7 due to SAE/drop out; likewise in the placebo group only 37 of 45 patients.
Clinical Global Impression of Severity (CGI-S) is a 7 item scale that requires the clinician to rate the severity of the patient's illness at the time of assessment.. Possible ratings are: 1. Normal, not at all ill 2. Borderline mentally ill 3. Mildly ill 4. Moderately ill 5. Markedly ill 6. Severely ill 7. Among the most extremely ill patients
Outcome measures
| Measure |
EGCG as Putative Neuroprotective Agent
n=23 Participants
Treatment with 800 mg - 1200 mg EGCG as putative neuroprotective agent
|
Placebo
n=37 Participants
Placebo
Placebo: Placebo
|
|---|---|---|
|
Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 7
severity of illness=1
|
0 participants
|
0 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 7
severity of illness=2
|
1 participants
|
0 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 7
severity of illness=3
|
2 participants
|
3 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 7
severity of illness=4
|
7 participants
|
9 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 7
severity of illness=5
|
9 participants
|
16 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 7
severity of illness=6
|
4 participants
|
8 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 7
severity of illness=7
|
0 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Visit 7: 52 weeks after baseline visitPopulation: Eligible patients were older than 30 years; met the diagnostic criteria for possible or probable parkinsonism-predominant or cerebellar-ataxia-predominant multiple system atrophy; could ambulate independently (ie, Hoehn and Yahr stages 1-3); and had to be on stable anti-Parkinson's, anti-dysautonomia, anti-dementia, and anti-depressant regimens. In the EGCG group only 32 of 47 patients provided data at visit 5 due to SAE/drop out; likewise in the placebo group only 35 of 45 patients.
The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. Compared to the patient's condition at baseline, this patient's condition has either improved or worsened or is unchanged, with a lower score meaning more improvement and a higher score less improvement or worsening respectively. The patient´s state compared to baseline is rated as: 1. Very much improved 2. much improved 3. Minimally improved 4. No change 5. Minimally worse 6. Much worse 7 = Very much worse
Outcome measures
| Measure |
EGCG as Putative Neuroprotective Agent
n=32 Participants
Treatment with 800 mg - 1200 mg EGCG as putative neuroprotective agent
|
Placebo
n=35 Participants
Placebo
Placebo: Placebo
|
|---|---|---|
|
Number of Participants Achieving Each Clinical Global Impression of Improvement (CGI-I): Improvement Level at Visit 7 Compared to the Baseline Visit
global improvement =5
|
7 participants
|
12 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Improvement (CGI-I): Improvement Level at Visit 7 Compared to the Baseline Visit
global improvement =1
|
0 participants
|
0 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Improvement (CGI-I): Improvement Level at Visit 7 Compared to the Baseline Visit
global improvement =2
|
0 participants
|
0 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Improvement (CGI-I): Improvement Level at Visit 7 Compared to the Baseline Visit
global improvement =3
|
4 participants
|
5 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Improvement (CGI-I): Improvement Level at Visit 7 Compared to the Baseline Visit
global improvement =4
|
10 participants
|
8 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Improvement (CGI-I): Improvement Level at Visit 7 Compared to the Baseline Visit
global improvement =6
|
8 participants
|
9 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Improvement (CGI-I): Improvement Level at Visit 7 Compared to the Baseline Visit
global improvement =7
|
3 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Visit 7: 52 weeks after baseline visitPopulation: Eligible patients were older than 30 years; met the diagnostic criteria for possible or probable parkinsonism-predominant or cerebellar-ataxia-predominant multiple system atrophy; could ambulate independently (ie, Hoehn and Yahr stages 1-3); and had to be on stable anti-Parkinson's, anti-dysautonomia, anti-dementia, and anti-depressant regimens. In the EGCG group only 32 of 47 patients provided data at visit 5 due to SAE/drop out; likewise in the placebo group only 30 of 45 patients.
The Clinical Global Impression - Efficacy Index is a 4×4 rating scale that assesses the therapeutic effect of treatment with psychiatric medication and associated side effects. It comprises 4 Items for the therapeutic effect: 1. Marked - Vast improvement. Complete or nearly complete remission of all symptoms 2. Moderate - Decided improvement. Partial remission of symptoms 3. Minimal - Slight improvement which doesn't alter status of care of patient 4. Unchanged or worse combined with 4 items of possible side effects: 1= None - no side effects (S.E.) 2= Side effects (S.E.) do not significantly interfere with patient's functioning 3= S.E. significantly interfere with patient's functioning 4= S. E. outweigh therapeutic effect The lowest total score (score 1) means vast improvement with no side effects; the highest total score (score 16) means unchanged or worse patient´s condition with side effects that outweigh the therapeutic effect.
Outcome measures
| Measure |
EGCG as Putative Neuroprotective Agent
n=32 Participants
Treatment with 800 mg - 1200 mg EGCG as putative neuroprotective agent
|
Placebo
n=30 Participants
Placebo
Placebo: Placebo
|
|---|---|---|
|
Number of Participants Achieving Each Clinical Global Impression of Improvement (CGI-I): Efficacy Index (Therapeutic Effect of Treatment With Medication and Associated Side Effects) at Visit 7 Compared to the Baseline Visit
efficacy index score 5 (moderate therapeutic effect - no side effects
|
0 participants
|
1 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Improvement (CGI-I): Efficacy Index (Therapeutic Effect of Treatment With Medication and Associated Side Effects) at Visit 7 Compared to the Baseline Visit
efficacy index score 7 (moderate therapeutic effect - side effects significantly interfering)
|
1 participants
|
0 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Improvement (CGI-I): Efficacy Index (Therapeutic Effect of Treatment With Medication and Associated Side Effects) at Visit 7 Compared to the Baseline Visit
efficacy index score 9 (minimal therapeutic effect - no side effects
|
1 participants
|
1 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Improvement (CGI-I): Efficacy Index (Therapeutic Effect of Treatment With Medication and Associated Side Effects) at Visit 7 Compared to the Baseline Visit
efficacy index score 11 (minimal therapeutic effect - side effects significantly interfering)
|
0 participants
|
1 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Improvement (CGI-I): Efficacy Index (Therapeutic Effect of Treatment With Medication and Associated Side Effects) at Visit 7 Compared to the Baseline Visit
efficacy index score 13 (unchanged or worse -no side effects)
|
28 participants
|
26 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Improvement (CGI-I): Efficacy Index (Therapeutic Effect of Treatment With Medication and Associated Side Effects) at Visit 7 Compared to the Baseline Visit
efficacy index score 14 (unchanged or worse -side effects not significantly interfering)
|
1 participants
|
0 participants
|
|
Number of Participants Achieving Each Clinical Global Impression of Improvement (CGI-I): Efficacy Index (Therapeutic Effect of Treatment With Medication and Associated Side Effects) at Visit 7 Compared to the Baseline Visit
efficacy index score 15 (unchanged or worse -side effects significantly interfering)
|
1 participants
|
1 participants
|
Adverse Events
EGCG as Putative Neuroprotective Agent
Placebo
Serious adverse events
| Measure |
EGCG as Putative Neuroprotective Agent
n=47 participants at risk
Treatment with 800 mg - 1200 mg EGCG as putative neuroprotective agent
EGCG as putative neuroprotective agent: Treatment with 800 mg - 1200 mg EGCG as putative neuroprotective agent
|
Placebo
n=45 participants at risk
Placebo
Placebo: Placebo
|
|---|---|---|
|
Hepatobiliary disorders
Hepatotoxicity
|
4.3%
2/47 • Number of events 2 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
0.00%
0/45 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia due to aspiration
|
6.4%
3/47 • Number of events 3 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
0.00%
0/45 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
|
General disorders
Death
|
8.5%
4/47 • Number of events 4 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
4.4%
2/45 • Number of events 2 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
2.1%
1/47 • Number of events 1 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
0.00%
0/45 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
|
Cardiac disorders
synkope
|
2.1%
1/47 • Number of events 1 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
2.2%
1/45 • Number of events 1 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
|
Gastrointestinal disorders
gastrointestinal disorders
|
10.6%
5/47 • Number of events 5 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
2.2%
1/45 • Number of events 1 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
|
Surgical and medical procedures
surgery
|
2.1%
1/47 • Number of events 1 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
6.7%
3/45 • Number of events 3 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
|
Injury, poisoning and procedural complications
fracture of femoral bone
|
2.1%
1/47 • Number of events 1 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
2.2%
1/45 • Number of events 1 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
|
Skin and subcutaneous tissue disorders
phlegmone hand
|
2.1%
1/47 • Number of events 1 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
0.00%
0/45 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
|
Renal and urinary disorders
UTI
|
0.00%
0/47 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
4.4%
2/45 • Number of events 2 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
|
Nervous system disorders
headache
|
2.1%
1/47 • Number of events 1 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
0.00%
0/45 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
|
General disorders
heatstroke and exsikkosis
|
2.1%
1/47 • Number of events 1 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
0.00%
0/45 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
|
General disorders
general worsening of overall health
|
0.00%
0/47 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
2.2%
1/45 • Number of events 1 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
Other adverse events
| Measure |
EGCG as Putative Neuroprotective Agent
n=47 participants at risk
Treatment with 800 mg - 1200 mg EGCG as putative neuroprotective agent
EGCG as putative neuroprotective agent: Treatment with 800 mg - 1200 mg EGCG as putative neuroprotective agent
|
Placebo
n=45 participants at risk
Placebo
Placebo: Placebo
|
|---|---|---|
|
Renal and urinary disorders
UTI
|
19.1%
9/47 • Number of events 14 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
26.7%
12/45 • Number of events 18 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
|
Renal and urinary disorders
urinary dysfunction
|
6.4%
3/47 • Number of events 3 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
13.3%
6/45 • Number of events 6 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
|
Nervous system disorders
dysarthria
|
0.00%
0/47 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
8.9%
4/45 • Number of events 4 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
|
Nervous system disorders
dysphagia
|
8.5%
4/47 • Number of events 5 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
0.00%
0/45 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
|
Nervous system disorders
falls
|
36.2%
17/47 • Number of events 26 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
37.8%
17/45 • Number of events 31 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
|
Nervous system disorders
worsening of parkinsonism, ataxia or autonomic dysfunction
|
21.3%
10/47 • Number of events 24 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
20.0%
9/45 • Number of events 17 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
|
Hepatobiliary disorders
hepatotoxicity
|
12.8%
6/47 • Number of events 6 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
0.00%
0/45 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
|
Nervous system disorders
orthostatic hypotension
|
6.4%
3/47 • Number of events 6 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
11.1%
5/45 • Number of events 5 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
|
Gastrointestinal disorders
gastrointestinal adverse event
|
36.2%
17/47 • Number of events 28 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
28.9%
13/45 • Number of events 21 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
|
Nervous system disorders
swallowing problems
|
6.4%
3/47 • Number of events 5 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
0.00%
0/45 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
|
Vascular disorders
edema
|
6.4%
3/47 • Number of events 3 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
6.7%
3/45 • Number of events 3 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
|
Psychiatric disorders
depression
|
10.6%
5/47 • Number of events 5 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
4.4%
2/45 • Number of events 2 • 52 weeks
Adverse events were grouped according to Medical Dictionary for Regulatory Activities (MedDRA) organ class. Serious adverse events were defined as adverse events that led to hospitalisation, discontinuation of study medication because of liver toxicity, or death.
|
Additional Information
Prof. Dr. Johannes Levin
Department of Neurology, Ludwig-Maximilians-University Munich, Munich, Germany
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60