Trial Outcomes & Findings for Targeting Oxidative Stress in Chronic Beryllium Disease (NCT NCT01088243)
NCT ID: NCT01088243
Last Updated: 2018-10-12
Results Overview
Primary endpoints are beryllium proliferation responses (BeLPT) in PBMCs (peripheral blood mononuclear cells) and BAL (bronchoalveolar lavage) cells. The BeLPT is a blood test that measures the immune response to beryllium exposure. If immune cells multiply in response to beryllium, this is considered an abnormal test results. If immune cells do not multiple, this is considered a normal test results. Results are reported as "stimulation index", which is a ratio of the number of cells grown with beryllium compared to the number of cells grown without beryllium. A value of 2.5 or less is considered normal, and a value greater than 2.5 is abnormal.
COMPLETED
PHASE1/PHASE2
18 participants
baseline and week 6
2018-10-12
Participant Flow
Participant milestones
| Measure |
Mesalamine
Mesalamine (5-ASA) 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
Mesalamine: Mesalamine (5-ASA) 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
|
Placebo
Sugar pill 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
Placebo: Sugar pill 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
|
|---|---|---|
|
Overall Study
STARTED
|
13
|
5
|
|
Overall Study
COMPLETED
|
12
|
5
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Mesalamine
Mesalamine (5-ASA) 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
Mesalamine: Mesalamine (5-ASA) 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
|
Placebo
Sugar pill 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
Placebo: Sugar pill 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
Baseline Characteristics
Targeting Oxidative Stress in Chronic Beryllium Disease
Baseline characteristics by cohort
| Measure |
Mesalamine
n=13 Participants
Mesalamine (5-ASA) 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
Mesalamine: Mesalamine (5-ASA) 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
|
Placebo
n=5 Participants
Sugar pill 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
Placebo: Sugar pill 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
|
Total
n=18 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
63.3 years
n=5 Participants
|
62.8 years
n=7 Participants
|
63.16 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
13 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Smoking Status
Never
|
5 Count of Participants
n=5 Participants
|
2 Count of Participants
n=7 Participants
|
7 Count of Participants
n=5 Participants
|
|
Smoking Status
Former
|
8 Count of Participants
n=5 Participants
|
3 Count of Participants
n=7 Participants
|
11 Count of Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: baseline and week 6Population: Because bronchoscopy was not required for participation, only three placebo and six 5-ASA-treated subjects underwent bronchoscopy and is reported under BAL.
Primary endpoints are beryllium proliferation responses (BeLPT) in PBMCs (peripheral blood mononuclear cells) and BAL (bronchoalveolar lavage) cells. The BeLPT is a blood test that measures the immune response to beryllium exposure. If immune cells multiply in response to beryllium, this is considered an abnormal test results. If immune cells do not multiple, this is considered a normal test results. Results are reported as "stimulation index", which is a ratio of the number of cells grown with beryllium compared to the number of cells grown without beryllium. A value of 2.5 or less is considered normal, and a value greater than 2.5 is abnormal.
Outcome measures
| Measure |
Mesalamine
n=13 Participants
Mesalamine (5-ASA) 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
Mesalamine: Mesalamine (5-ASA) 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
|
Placebo
n=5 Participants
Sugar pill 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
Placebo: Sugar pill 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
|
|---|---|---|
|
Change in Beryllium Lymphocyte Proliferation Responses (BeLPT) From Baseline to Week 6
BAL
|
48.61 Stimulation index
Standard Deviation 57.18
|
9.33 Stimulation index
Standard Deviation 14.08
|
|
Change in Beryllium Lymphocyte Proliferation Responses (BeLPT) From Baseline to Week 6
PBMC
|
22.07 Stimulation index
Standard Deviation 20.30
|
3.8 Stimulation index
Standard Deviation 6.09
|
SECONDARY outcome
Timeframe: baseline and week 6Population: We did not have sufficient cells to run experiments on all participants. However, below is a summary of what data was received.
Secondary outcomes include changes in bronchoalveolar lavage (BAL) tumor necrosis factor alpha (TNFa)
Outcome measures
| Measure |
Mesalamine
n=6 Participants
Mesalamine (5-ASA) 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
Mesalamine: Mesalamine (5-ASA) 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
|
Placebo
n=3 Participants
Sugar pill 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
Placebo: Sugar pill 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
|
|---|---|---|
|
Changes in Bronchoalveolar Lavage (BAL) Tumor Necrosis Factor Alpha (TNFa)
|
62 pg/ml
Standard Deviation 35.76
|
-1750 pg/ml
Standard Deviation 2734
|
SECONDARY outcome
Timeframe: baseline and week 6Population: We did not receive enough cells from participants to be able to run experiments on all. However, below is a summary of what data was received.
Secondary outcomes include changes in steady-state GSH levels in beryllium specific CD4+ T cell in bronchoalveolar lavage fluid (BALF)
Outcome measures
| Measure |
Mesalamine
n=6 Participants
Mesalamine (5-ASA) 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
Mesalamine: Mesalamine (5-ASA) 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
|
Placebo
n=3 Participants
Sugar pill 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
Placebo: Sugar pill 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
|
|---|---|---|
|
Changes in Steady-state Glutathione (GSH) Levels From Baseline to Week 6
|
4.93 mmol/mg
Standard Deviation 20.08
|
10.38 mmol/mg
Standard Deviation 16.5
|
SECONDARY outcome
Timeframe: baseline and week 6Population: We were not able to perform due to insufficient samples and data collected from each participant to summarize changes in HDAC2 levels.
Secondary outcomes include changes in HDAC2 levels
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: baseline and week 6Population: We were not able to perform due to insufficient samples and data collected from each participant to summarize changes.
Secondary outcomes include changes in glucocorticoid receptors modification in PBMCs and BAL cells.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: baseline and week 6Population: One participant did not complete follow up in Mesalamine group. However, below is a summary of what data was received.
Secondary outcomes include changes in lung function, which will be assessed with Forced expiratory volume in 1 second percent predicted (FEV1), Forced vital capacity percent predicted (FVC) and Diffusing capacity percent predicted (DLCO).
Outcome measures
| Measure |
Mesalamine
n=12 Participants
Mesalamine (5-ASA) 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
Mesalamine: Mesalamine (5-ASA) 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
|
Placebo
n=5 Participants
Sugar pill 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
Placebo: Sugar pill 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
|
|---|---|---|
|
Lung Function
FEV1 % pred
|
2.2 percentage of predicted value
Standard Deviation 4.49
|
-0.91 percentage of predicted value
Standard Deviation 4.73
|
|
Lung Function
FVC % pred
|
1.6 percentage of predicted value
Standard Deviation 3.5
|
-0.08 percentage of predicted value
Standard Deviation 5.55
|
|
Lung Function
DLCO % pred
|
2.4 percentage of predicted value
Standard Deviation 4.39
|
-0.16 percentage of predicted value
Standard Deviation 6.01
|
Adverse Events
Mesalamine
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Mesalamine
n=13 participants at risk
Mesalamine (5-ASA) 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
Mesalamine: Mesalamine (5-ASA) 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
|
Placebo
n=5 participants at risk
Sugar pill 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
Placebo: Sugar pill 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
|
|---|---|---|
|
Cardiac disorders
Mobitz Type II heart block
|
0.00%
0/13 • The patients will be monitored after baseline evaluation, during drug therapy, and after 2 week follow-up evaluation by a study coordinator and Dr. Maier who will follow-up for adverse events at each visit. All adverse events (serious and moderate/mild) associated with bronchoscopy procedures and study drug will be assessed individually by study PIs for appropriate action if necessary.
|
20.0%
1/5 • Number of events 1 • The patients will be monitored after baseline evaluation, during drug therapy, and after 2 week follow-up evaluation by a study coordinator and Dr. Maier who will follow-up for adverse events at each visit. All adverse events (serious and moderate/mild) associated with bronchoscopy procedures and study drug will be assessed individually by study PIs for appropriate action if necessary.
|
|
Skin and subcutaneous tissue disorders
Swelling
|
0.00%
0/13 • The patients will be monitored after baseline evaluation, during drug therapy, and after 2 week follow-up evaluation by a study coordinator and Dr. Maier who will follow-up for adverse events at each visit. All adverse events (serious and moderate/mild) associated with bronchoscopy procedures and study drug will be assessed individually by study PIs for appropriate action if necessary.
|
20.0%
1/5 • Number of events 1 • The patients will be monitored after baseline evaluation, during drug therapy, and after 2 week follow-up evaluation by a study coordinator and Dr. Maier who will follow-up for adverse events at each visit. All adverse events (serious and moderate/mild) associated with bronchoscopy procedures and study drug will be assessed individually by study PIs for appropriate action if necessary.
|
|
General disorders
One 5-ASA-treated subject developed dizziness, constipation, stomach pain and chest pain two weeks
|
7.7%
1/13 • Number of events 1 • The patients will be monitored after baseline evaluation, during drug therapy, and after 2 week follow-up evaluation by a study coordinator and Dr. Maier who will follow-up for adverse events at each visit. All adverse events (serious and moderate/mild) associated with bronchoscopy procedures and study drug will be assessed individually by study PIs for appropriate action if necessary.
|
0.00%
0/5 • The patients will be monitored after baseline evaluation, during drug therapy, and after 2 week follow-up evaluation by a study coordinator and Dr. Maier who will follow-up for adverse events at each visit. All adverse events (serious and moderate/mild) associated with bronchoscopy procedures and study drug will be assessed individually by study PIs for appropriate action if necessary.
|
|
General disorders
One 5-ASA-treated subject experienced coughing and low energy after the follow-up bronchoscopy
|
7.7%
1/13 • Number of events 1 • The patients will be monitored after baseline evaluation, during drug therapy, and after 2 week follow-up evaluation by a study coordinator and Dr. Maier who will follow-up for adverse events at each visit. All adverse events (serious and moderate/mild) associated with bronchoscopy procedures and study drug will be assessed individually by study PIs for appropriate action if necessary.
|
0.00%
0/5 • The patients will be monitored after baseline evaluation, during drug therapy, and after 2 week follow-up evaluation by a study coordinator and Dr. Maier who will follow-up for adverse events at each visit. All adverse events (serious and moderate/mild) associated with bronchoscopy procedures and study drug will be assessed individually by study PIs for appropriate action if necessary.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place