Trial Outcomes & Findings for Biomarkers of Lupus Disease: Serial Biomarker Sampling in Patients With Active Systemic Lupus Erythematosus (SLE) (NCT NCT00987831)
NCT ID: NCT00987831
Last Updated: 2014-10-20
Results Overview
Group A only: patients on immunosuppressive treatments had them withdrawn at baseline. All patients were allowed up to 160 mg depomedrol at baseline which could be repeated within two weeks up to a total of 4 shots maximum or until satisfactory improvement. Time to flare was calculated from baseline. moderate disease at baseline was defined as up to 3 BILAG B (moderate disease) organ scores, no BILAG A (severe disease) score and a SLEDAI \</= 10. Severe disease required \>3 BILAG B, OR at least one BILAG A OR SLEDAI \> 10 or meeting criteria for a severe flare on the SELENA SLEDAI flare index. At baseline 25 patients with moderate disease. 16 patients had severe disease. Note: severe rash with A on BILAG is only SLEDAI=2, explaining some discrepancies in measures
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
158 participants
Primary outcome timeframe
12 months
Results posted on
2014-10-20
Participant Flow
The final recruitment tally is as follows: 41 SLE patients entered the prospective serial blood donation study. 62 SLE patients gave one time blood sample and 52 controls gave two blood samples each
All patients in Group A (prospective study) had any immune suppressive (e.g. MMF, MTX, AZA) withdrawn at the time of entry and all received between 1-3 depomedrol shots up to 160 mg each. Those who did not improve were immediately withdrawn from prospective study but the original sample was retained, in all cases, for the cross sectional arm.
Participant milestones
| Measure |
Group A Medication Withdrawal, Depomedrol, Prospective Follow-
When depomedrol was given, any immune suppressant being taken (e.g. aza, mmf, mtx) was stopped and biomarkers studied before and after this change. Depomedrol was expected to last 1-3 months, serial biomarkers were drawn until time of any flare, designated as end of study. Patients could elect to continue to donate blood samples per protocol up to one year. Of 41 patients who improved after depomedrol and could complete Group A, 40 flared at or before the six month visit. One patient continued for one year and did not flare. This study design allowed the comparison of 40 patients flaring at baseline on or not on background immune suppression vs themselves serving as their own control flaring later....not on immune suppression.
|
Group C Healthy Controls
Healthy controls, age, sex and ethnicity matched to SLE study participants were recruited for two time blood donation as controls for the biomarker studies
Blood drawing and brief history only : No treatments given
|
Group B SLE One Time Donation
We amended protocol with IRB approval to include more patients in this group and ended up recruiting a total of 62. This was to allow enrichment of a cross sectional study of biomarkers related to the different background immune suppressants used in Group A at baseline. By combining baseline samples from Group A and Group B data we had a total of 103 lupus samples to study cross sectionally comparing impact of methotrexate, mmf, azathioprine or no IS on a range of biomarkers.
|
|---|---|---|---|
|
Overall Study
STARTED
|
41
|
55
|
62
|
|
Overall Study
COMPLETED
|
40
|
52
|
62
|
|
Overall Study
NOT COMPLETED
|
1
|
3
|
0
|
Reasons for withdrawal
| Measure |
Group A Medication Withdrawal, Depomedrol, Prospective Follow-
When depomedrol was given, any immune suppressant being taken (e.g. aza, mmf, mtx) was stopped and biomarkers studied before and after this change. Depomedrol was expected to last 1-3 months, serial biomarkers were drawn until time of any flare, designated as end of study. Patients could elect to continue to donate blood samples per protocol up to one year. Of 41 patients who improved after depomedrol and could complete Group A, 40 flared at or before the six month visit. One patient continued for one year and did not flare. This study design allowed the comparison of 40 patients flaring at baseline on or not on background immune suppression vs themselves serving as their own control flaring later....not on immune suppression.
|
Group C Healthy Controls
Healthy controls, age, sex and ethnicity matched to SLE study participants were recruited for two time blood donation as controls for the biomarker studies
Blood drawing and brief history only : No treatments given
|
Group B SLE One Time Donation
We amended protocol with IRB approval to include more patients in this group and ended up recruiting a total of 62. This was to allow enrichment of a cross sectional study of biomarkers related to the different background immune suppressants used in Group A at baseline. By combining baseline samples from Group A and Group B data we had a total of 103 lupus samples to study cross sectionally comparing impact of methotrexate, mmf, azathioprine or no IS on a range of biomarkers.
|
|---|---|---|---|
|
Overall Study
Never flared in 12 months
|
1
|
0
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
3
|
0
|
Baseline Characteristics
Biomarkers of Lupus Disease: Serial Biomarker Sampling in Patients With Active Systemic Lupus Erythematosus (SLE)
Baseline characteristics by cohort
| Measure |
Group A Medication Withdrawal, Depomedrol, Prospective Follow-
n=41 Participants
When depomedrol was given, any immune suppressant being taken (e.g. aza, mmf, mtx) was stopped and biomarkers studied before and after this change. Depomedrol was expected to last 1-3 months, serial biomarkers were drawn until time of any flare, designated as end of study. Patients could elect to continue to donate blood samples per protocol up to one year. Of 41 patients who improved after depomedrol and could complete Group A, 40 flared at or before the six month visit. One patient continued for one year and did not flare. This study design allowed the comparison of 40 patients flaring at baseline on or not on background immune suppresion vs themselves serving as their own control flaring later....not on immune suppression.
|
Group C Healthy Controls
n=55 Participants
Healthy controls, age, sex and ethnicity matched to SLE study participants were recruited for two time blood donation as controls for the biomarker studies
Blood drawing and brief history only : No treatments given
|
Group B SLE One Time Donation
n=62 Participants
We amended protocol with IRB approval to include more patients in this group and ended up recruiting a total of 62. This was to allow enrichment of a cross sectional study of biomarkers related to the different background immune suppressants used in Group A at baseline. By combining baseline samples from Group A and Group B data we had a total of 103 lupus samples to study cross sectionally comparing impact of methotrexate, mmf, azathioprine or no IS on a range of biomarkers.
|
Total
n=158 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
40 Participants
n=5 Participants
|
55 Participants
n=7 Participants
|
62 Participants
n=5 Participants
|
157 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Age, Continuous
|
42.3 years
STANDARD_DEVIATION 11.9 • n=5 Participants
|
40.8 years
STANDARD_DEVIATION 12.1 • n=7 Participants
|
41.6 years
STANDARD_DEVIATION 11.3 • n=5 Participants
|
41.1 years
STANDARD_DEVIATION 11.7 • n=4 Participants
|
|
Sex: Female, Male
Female
|
39 Participants
n=5 Participants
|
53 Participants
n=7 Participants
|
55 Participants
n=5 Participants
|
147 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
41 participants
n=5 Participants
|
55 participants
n=7 Participants
|
62 participants
n=5 Participants
|
158 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 12 monthsPopulation: This prespecified primary outcome was restricted to Group A only. This was an exploratory proof of concept study, not powered for the primary endpoint
Group A only: patients on immunosuppressive treatments had them withdrawn at baseline. All patients were allowed up to 160 mg depomedrol at baseline which could be repeated within two weeks up to a total of 4 shots maximum or until satisfactory improvement. Time to flare was calculated from baseline. moderate disease at baseline was defined as up to 3 BILAG B (moderate disease) organ scores, no BILAG A (severe disease) score and a SLEDAI \</= 10. Severe disease required \>3 BILAG B, OR at least one BILAG A OR SLEDAI \> 10 or meeting criteria for a severe flare on the SELENA SLEDAI flare index. At baseline 25 patients with moderate disease. 16 patients had severe disease. Note: severe rash with A on BILAG is only SLEDAI=2, explaining some discrepancies in measures
Outcome measures
| Measure |
Severe Disease Activity at Baseline
n=16 Participants
This is fully explained above. Severe disease activity is defined as \> 3 BILAG B, OR at least one BILAG A or SLEDAI \> 10 OR Meets Definition for severe Flare on SELENA SLEDAI
|
Moderate Disease Activity at Baseline
n=25 Participants
this is fully explained above. Moderate disease activity is defined as up to 3 BILAG B, no A, and SLEDAI \</= 10.
|
|---|---|---|
|
Time to Flare Comparing Patients With Moderate vs Severe Disease Activity at Baseline
|
45 days to flare
Interval 30.0 to 91.0
|
71 days to flare
Interval 43.0 to 91.0
|
POST_HOC outcome
Timeframe: 12 monthsPopulation: Only 40/41 entered patients completed the study by the definition of the endpoint which was flare.
Outcome measures
| Measure |
Severe Disease Activity at Baseline
n=11 Participants
This is fully explained above. Severe disease activity is defined as \> 3 BILAG B, OR at least one BILAG A or SLEDAI \> 10 OR Meets Definition for severe Flare on SELENA SLEDAI
|
Moderate Disease Activity at Baseline
n=29 Participants
this is fully explained above. Moderate disease activity is defined as up to 3 BILAG B, no A, and SLEDAI \</= 10.
|
|---|---|---|
|
Time to Flare Comparing Patients With (at Baseline) British Isles Lupus Assessment Group Index (BILAG) >/= 17 (Severe Disease) to Those With BILAG < 17 (Moderate Disease Activity).
|
40 days to flare
Interval 29.0 to 72.0
|
72.5 days to flare
Interval 46.0 to 99.0
|
Adverse Events
Group A Medication Withdrawal, Depomedrol, Prospective Follow-
Serious events: 1 serious events
Other events: 29 other events
Deaths: 0 deaths
Group C Healthy Controls
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Group B SLE One Time Donation
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Group A Medication Withdrawal, Depomedrol, Prospective Follow-
n=41 participants at risk
When depomedrol was given, any immune suppressant being taken (e.g. aza, mmf, mtx) was stopped and biomarkers studied before and after this change. Depomedrol was expected to last 1-3 months, serial biomarkers were drawn until time of any flare, designated as end of study. Patients could elect to continue to donate blood samples per protocol up to one year. Of 41 patients who improved after depomedrol and could complete Group A, 40 flared at or before the six month visit. One patient continued for one year and did not flare. This study design allowed the comparison of 40 patients flaring at baseline on or not on background immune suppression vs themselves serving as their own control flaring later....not on immune suppression.
|
Group C Healthy Controls
n=55 participants at risk
Healthy controls, age, sex and ethnicity matched to SLE study participants were recruited for two time blood donation as controls for the biomarker studies
Blood drawing and brief history only : No treatments given
|
Group B SLE One Time Donation
n=62 participants at risk
We amended protocol with IRB approval to include more patients in this group and ended up recruiting a total of 62. This was to allow enrichment of a cross sectional study of biomarkers related to the different background immune suppressants used in Group A at baseline. By combining baseline samples from Group A and Group B data we had a total of 103 lupus samples to study cross sectionally comparing impact of methotrexate, mmf, azathioprine or no IS on a range of biomarkers.
|
|---|---|---|---|
|
Gastrointestinal disorders
Bleeding Peptic Ulcer
|
2.4%
1/41 • Number of events 1 • Adverse events were collected until end of study participation (ranging one visit to 12 months) Note all patients in Group A who flared were treated and followed up within six weeks and all improved again on new treatments initiated at the time of flare.
This was an interventional study using depomedrol which is a commonly used treatment in our clinic. The main safety issue in the study was the withdrawal of background immune suppressants.
|
0.00%
0/55 • Adverse events were collected until end of study participation (ranging one visit to 12 months) Note all patients in Group A who flared were treated and followed up within six weeks and all improved again on new treatments initiated at the time of flare.
This was an interventional study using depomedrol which is a commonly used treatment in our clinic. The main safety issue in the study was the withdrawal of background immune suppressants.
|
0.00%
0/62 • Adverse events were collected until end of study participation (ranging one visit to 12 months) Note all patients in Group A who flared were treated and followed up within six weeks and all improved again on new treatments initiated at the time of flare.
This was an interventional study using depomedrol which is a commonly used treatment in our clinic. The main safety issue in the study was the withdrawal of background immune suppressants.
|
Other adverse events
| Measure |
Group A Medication Withdrawal, Depomedrol, Prospective Follow-
n=41 participants at risk
When depomedrol was given, any immune suppressant being taken (e.g. aza, mmf, mtx) was stopped and biomarkers studied before and after this change. Depomedrol was expected to last 1-3 months, serial biomarkers were drawn until time of any flare, designated as end of study. Patients could elect to continue to donate blood samples per protocol up to one year. Of 41 patients who improved after depomedrol and could complete Group A, 40 flared at or before the six month visit. One patient continued for one year and did not flare. This study design allowed the comparison of 40 patients flaring at baseline on or not on background immune suppression vs themselves serving as their own control flaring later....not on immune suppression.
|
Group C Healthy Controls
n=55 participants at risk
Healthy controls, age, sex and ethnicity matched to SLE study participants were recruited for two time blood donation as controls for the biomarker studies
Blood drawing and brief history only : No treatments given
|
Group B SLE One Time Donation
n=62 participants at risk
We amended protocol with IRB approval to include more patients in this group and ended up recruiting a total of 62. This was to allow enrichment of a cross sectional study of biomarkers related to the different background immune suppressants used in Group A at baseline. By combining baseline samples from Group A and Group B data we had a total of 103 lupus samples to study cross sectionally comparing impact of methotrexate, mmf, azathioprine or no IS on a range of biomarkers.
|
|---|---|---|---|
|
Infections and infestations
Upper Respiratory Infection
|
7.3%
3/41 • Number of events 3 • Adverse events were collected until end of study participation (ranging one visit to 12 months) Note all patients in Group A who flared were treated and followed up within six weeks and all improved again on new treatments initiated at the time of flare.
This was an interventional study using depomedrol which is a commonly used treatment in our clinic. The main safety issue in the study was the withdrawal of background immune suppressants.
|
0.00%
0/55 • Adverse events were collected until end of study participation (ranging one visit to 12 months) Note all patients in Group A who flared were treated and followed up within six weeks and all improved again on new treatments initiated at the time of flare.
This was an interventional study using depomedrol which is a commonly used treatment in our clinic. The main safety issue in the study was the withdrawal of background immune suppressants.
|
0.00%
0/62 • Adverse events were collected until end of study participation (ranging one visit to 12 months) Note all patients in Group A who flared were treated and followed up within six weeks and all improved again on new treatments initiated at the time of flare.
This was an interventional study using depomedrol which is a commonly used treatment in our clinic. The main safety issue in the study was the withdrawal of background immune suppressants.
|
|
Infections and infestations
sinusitis
|
9.8%
4/41 • Number of events 4 • Adverse events were collected until end of study participation (ranging one visit to 12 months) Note all patients in Group A who flared were treated and followed up within six weeks and all improved again on new treatments initiated at the time of flare.
This was an interventional study using depomedrol which is a commonly used treatment in our clinic. The main safety issue in the study was the withdrawal of background immune suppressants.
|
0.00%
0/55 • Adverse events were collected until end of study participation (ranging one visit to 12 months) Note all patients in Group A who flared were treated and followed up within six weeks and all improved again on new treatments initiated at the time of flare.
This was an interventional study using depomedrol which is a commonly used treatment in our clinic. The main safety issue in the study was the withdrawal of background immune suppressants.
|
0.00%
0/62 • Adverse events were collected until end of study participation (ranging one visit to 12 months) Note all patients in Group A who flared were treated and followed up within six weeks and all improved again on new treatments initiated at the time of flare.
This was an interventional study using depomedrol which is a commonly used treatment in our clinic. The main safety issue in the study was the withdrawal of background immune suppressants.
|
|
Renal and urinary disorders
urinary tract infection
|
4.9%
2/41 • Number of events 2 • Adverse events were collected until end of study participation (ranging one visit to 12 months) Note all patients in Group A who flared were treated and followed up within six weeks and all improved again on new treatments initiated at the time of flare.
This was an interventional study using depomedrol which is a commonly used treatment in our clinic. The main safety issue in the study was the withdrawal of background immune suppressants.
|
0.00%
0/55 • Adverse events were collected until end of study participation (ranging one visit to 12 months) Note all patients in Group A who flared were treated and followed up within six weeks and all improved again on new treatments initiated at the time of flare.
This was an interventional study using depomedrol which is a commonly used treatment in our clinic. The main safety issue in the study was the withdrawal of background immune suppressants.
|
0.00%
0/62 • Adverse events were collected until end of study participation (ranging one visit to 12 months) Note all patients in Group A who flared were treated and followed up within six weeks and all improved again on new treatments initiated at the time of flare.
This was an interventional study using depomedrol which is a commonly used treatment in our clinic. The main safety issue in the study was the withdrawal of background immune suppressants.
|
|
Gastrointestinal disorders
gastroenteritis
|
19.5%
8/41 • Number of events 8 • Adverse events were collected until end of study participation (ranging one visit to 12 months) Note all patients in Group A who flared were treated and followed up within six weeks and all improved again on new treatments initiated at the time of flare.
This was an interventional study using depomedrol which is a commonly used treatment in our clinic. The main safety issue in the study was the withdrawal of background immune suppressants.
|
0.00%
0/55 • Adverse events were collected until end of study participation (ranging one visit to 12 months) Note all patients in Group A who flared were treated and followed up within six weeks and all improved again on new treatments initiated at the time of flare.
This was an interventional study using depomedrol which is a commonly used treatment in our clinic. The main safety issue in the study was the withdrawal of background immune suppressants.
|
0.00%
0/62 • Adverse events were collected until end of study participation (ranging one visit to 12 months) Note all patients in Group A who flared were treated and followed up within six weeks and all improved again on new treatments initiated at the time of flare.
This was an interventional study using depomedrol which is a commonly used treatment in our clinic. The main safety issue in the study was the withdrawal of background immune suppressants.
|
|
Infections and infestations
oral candidiasis
|
4.9%
2/41 • Number of events 2 • Adverse events were collected until end of study participation (ranging one visit to 12 months) Note all patients in Group A who flared were treated and followed up within six weeks and all improved again on new treatments initiated at the time of flare.
This was an interventional study using depomedrol which is a commonly used treatment in our clinic. The main safety issue in the study was the withdrawal of background immune suppressants.
|
0.00%
0/55 • Adverse events were collected until end of study participation (ranging one visit to 12 months) Note all patients in Group A who flared were treated and followed up within six weeks and all improved again on new treatments initiated at the time of flare.
This was an interventional study using depomedrol which is a commonly used treatment in our clinic. The main safety issue in the study was the withdrawal of background immune suppressants.
|
0.00%
0/62 • Adverse events were collected until end of study participation (ranging one visit to 12 months) Note all patients in Group A who flared were treated and followed up within six weeks and all improved again on new treatments initiated at the time of flare.
This was an interventional study using depomedrol which is a commonly used treatment in our clinic. The main safety issue in the study was the withdrawal of background immune suppressants.
|
|
Endocrine disorders
cushingoid face
|
4.9%
2/41 • Number of events 2 • Adverse events were collected until end of study participation (ranging one visit to 12 months) Note all patients in Group A who flared were treated and followed up within six weeks and all improved again on new treatments initiated at the time of flare.
This was an interventional study using depomedrol which is a commonly used treatment in our clinic. The main safety issue in the study was the withdrawal of background immune suppressants.
|
0.00%
0/55 • Adverse events were collected until end of study participation (ranging one visit to 12 months) Note all patients in Group A who flared were treated and followed up within six weeks and all improved again on new treatments initiated at the time of flare.
This was an interventional study using depomedrol which is a commonly used treatment in our clinic. The main safety issue in the study was the withdrawal of background immune suppressants.
|
0.00%
0/62 • Adverse events were collected until end of study participation (ranging one visit to 12 months) Note all patients in Group A who flared were treated and followed up within six weeks and all improved again on new treatments initiated at the time of flare.
This was an interventional study using depomedrol which is a commonly used treatment in our clinic. The main safety issue in the study was the withdrawal of background immune suppressants.
|
|
Nervous system disorders
insomnia
|
9.8%
4/41 • Number of events 4 • Adverse events were collected until end of study participation (ranging one visit to 12 months) Note all patients in Group A who flared were treated and followed up within six weeks and all improved again on new treatments initiated at the time of flare.
This was an interventional study using depomedrol which is a commonly used treatment in our clinic. The main safety issue in the study was the withdrawal of background immune suppressants.
|
0.00%
0/55 • Adverse events were collected until end of study participation (ranging one visit to 12 months) Note all patients in Group A who flared were treated and followed up within six weeks and all improved again on new treatments initiated at the time of flare.
This was an interventional study using depomedrol which is a commonly used treatment in our clinic. The main safety issue in the study was the withdrawal of background immune suppressants.
|
0.00%
0/62 • Adverse events were collected until end of study participation (ranging one visit to 12 months) Note all patients in Group A who flared were treated and followed up within six weeks and all improved again on new treatments initiated at the time of flare.
This was an interventional study using depomedrol which is a commonly used treatment in our clinic. The main safety issue in the study was the withdrawal of background immune suppressants.
|
|
Immune system disorders
seasonal allergy
|
4.9%
2/41 • Number of events 2 • Adverse events were collected until end of study participation (ranging one visit to 12 months) Note all patients in Group A who flared were treated and followed up within six weeks and all improved again on new treatments initiated at the time of flare.
This was an interventional study using depomedrol which is a commonly used treatment in our clinic. The main safety issue in the study was the withdrawal of background immune suppressants.
|
0.00%
0/55 • Adverse events were collected until end of study participation (ranging one visit to 12 months) Note all patients in Group A who flared were treated and followed up within six weeks and all improved again on new treatments initiated at the time of flare.
This was an interventional study using depomedrol which is a commonly used treatment in our clinic. The main safety issue in the study was the withdrawal of background immune suppressants.
|
0.00%
0/62 • Adverse events were collected until end of study participation (ranging one visit to 12 months) Note all patients in Group A who flared were treated and followed up within six weeks and all improved again on new treatments initiated at the time of flare.
This was an interventional study using depomedrol which is a commonly used treatment in our clinic. The main safety issue in the study was the withdrawal of background immune suppressants.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
4.9%
2/41 • Number of events 2 • Adverse events were collected until end of study participation (ranging one visit to 12 months) Note all patients in Group A who flared were treated and followed up within six weeks and all improved again on new treatments initiated at the time of flare.
This was an interventional study using depomedrol which is a commonly used treatment in our clinic. The main safety issue in the study was the withdrawal of background immune suppressants.
|
0.00%
0/55 • Adverse events were collected until end of study participation (ranging one visit to 12 months) Note all patients in Group A who flared were treated and followed up within six weeks and all improved again on new treatments initiated at the time of flare.
This was an interventional study using depomedrol which is a commonly used treatment in our clinic. The main safety issue in the study was the withdrawal of background immune suppressants.
|
0.00%
0/62 • Adverse events were collected until end of study participation (ranging one visit to 12 months) Note all patients in Group A who flared were treated and followed up within six weeks and all improved again on new treatments initiated at the time of flare.
This was an interventional study using depomedrol which is a commonly used treatment in our clinic. The main safety issue in the study was the withdrawal of background immune suppressants.
|
Additional Information
Joan T Merrill, M.D
Oklahoma Medical Research Foundation
Phone: 405-271-7805
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60