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Trial record 5 of 117 for:    "Connective Tissue Disease" | "Methylprednisolone"

Biomarkers of Lupus Disease: Serial Biomarker Sampling in Patients With Active Systemic Lupus Erythematosus (SLE) (BOLD)

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ClinicalTrials.gov Identifier: NCT00987831
Recruitment Status : Completed
First Posted : October 1, 2009
Results First Posted : October 20, 2014
Last Update Posted : October 20, 2014
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Joan Merrill, MD, Oklahoma Medical Research Foundation

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Systemic Lupus Erythematosus
Interventions Other: Group B SLE one blood donation
Other: Blood drawing only Group C
Drug: Group A SLE prospective study
Enrollment 158
Recruitment Details 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
Pre-assignment Details All patients in Group A (prospective study) had any immune suppressive (e.g. MMF, MTX, AZA) withdrawn at the time of entry and all received between 1-3 depomedrol shots up to 160 mg each. Those who did not improve were immediately withdrawn from prospective study but the original sample was retained, in all cases, for the cross sectional arm.
Arm/Group Title Group A Medication Withdrawal, Depomedrol, Prospective Follow- Group C Healthy Controls Group B SLE One Time Donation
Hide Arm/Group Description 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.

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

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.
Period Title: Overall Study
Started 41 [1] 55 [2] 62 [3]
Completed 40 [4] 52 [5] 62 [3]
Not Completed 1 3 0
Reason Not Completed
Never flared in 12 months             1             0             0
Lost to Follow-up             0             3             0
[1]
41 patients improved after depomedrol, if not improved, treated and moved to Group B
[2]
52 healthy controls donated biomarkers on two occasions in order to verify biomarkers ranges
[3]
Anyone who entered this arm completed it the same day
[4]
40 patients completed in 6 months. 1 patient did not meet completion definition in 12 months.
[5]
all controls returned for two visits
Arm/Group Title Group A Medication Withdrawal, Depomedrol, Prospective Follow- Group C Healthy Controls Group B SLE One Time Donation Total
Hide Arm/Group Description 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.

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

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 of all reporting groups
Overall Number of Baseline Participants 41 55 62 158
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants 55 participants 62 participants 158 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
40
  97.6%
55
 100.0%
62
 100.0%
157
  99.4%
>=65 years
1
   2.4%
0
   0.0%
0
   0.0%
1
   0.6%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 41 participants 55 participants 62 participants 158 participants
42.3  (11.9) 40.8  (12.1) 41.6  (11.3) 41.1  (11.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants 55 participants 62 participants 158 participants
Female
39
  95.1%
53
  96.4%
55
  88.7%
147
  93.0%
Male
2
   4.9%
2
   3.6%
7
  11.3%
11
   7.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 41 participants 55 participants 62 participants 158 participants
41 55 62 158
1.Primary Outcome
Title Time to Flare Comparing Patients With Moderate vs Severe Disease Activity at Baseline
Hide Description 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
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
This prespecified primary outcome was restricted to Group A only. This was an exploratory proof of concept study, not powered for the primary endpoint
Arm/Group Title Severe Disease Activity at Baseline Moderate Disease Activity at Baseline
Hide Arm/Group Description:
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
this is fully explained above. Moderate disease activity is defined as up to 3 BILAG B, no A, and SLEDAI </= 10.
Overall Number of Participants Analyzed 16 25
Median (95% Confidence Interval)
Unit of Measure: days to flare
45
(30 to 91)
71
(43 to 91)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Severe Disease Activity at Baseline, Moderate Disease Activity at Baseline
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2738
Comments Definition of Moderate Disease was </= 3 BILAG B (moderate) organ scores, no A (severe) scores and SLEDAI </=10. Severe disease was > 3 BILAG B or >/= BILAG A or SLEDAI > 10 or meets definition for severe flare on the SELENA SLEDAI Flare Index
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 30
Confidence Interval (2-Sided) 95%
5 to 95
Estimation Comments [Not Specified]
2.Post-Hoc Outcome
Title 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).
Hide Description [Not Specified]
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Only 40/41 entered patients completed the study by the definition of the endpoint which was flare.
Arm/Group Title Severe Disease Activity at Baseline Moderate Disease Activity at Baseline
Hide Arm/Group Description:
This is fully explained above. Severe disease is now defined as total cumulative BILAG score >/= 17
this is fully explained above. Moderate disease is now defined as BILAG < 17 in cumulative score
Overall Number of Participants Analyzed 11 29
Median (95% Confidence Interval)
Unit of Measure: days to flare
40
(29 to 72)
72.5
(46 to 99)
Time Frame 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.
Adverse Event Reporting Description 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.
 
Arm/Group Title Group A Medication Withdrawal, Depomedrol, Prospective Follow- Group C Healthy Controls Group B SLE One Time Donation
Hide Arm/Group Description 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.

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

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.
All-Cause Mortality
Group A Medication Withdrawal, Depomedrol, Prospective Follow- Group C Healthy Controls Group B SLE One Time Donation
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Group A Medication Withdrawal, Depomedrol, Prospective Follow- Group C Healthy Controls Group B SLE One Time Donation
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/41 (2.44%)      0/55 (0.00%)      0/62 (0.00%)    
Gastrointestinal disorders       
Bleeding Peptic Ulcer * [1]  1/41 (2.44%)  1 0/55 (0.00%)  0 0/62 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
[1]
The patient developed severe abdominal pain and was hospitalized for four days. Found to have an actively bleeding peptic ulcer. She recovered completely with supportive care and medications.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Group A Medication Withdrawal, Depomedrol, Prospective Follow- Group C Healthy Controls Group B SLE One Time Donation
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   29/41 (70.73%)      0/55 (0.00%)      0/62 (0.00%)    
Endocrine disorders       
cushingoid face * [1]  2/41 (4.88%)  2 0/55 (0.00%)  0 0/62 (0.00%)  0
Gastrointestinal disorders       
gastroenteritis * [2]  8/41 (19.51%)  8 0/55 (0.00%)  0 0/62 (0.00%)  0
Immune system disorders       
seasonal allergy * [3]  2/41 (4.88%)  2 0/55 (0.00%)  0 0/62 (0.00%)  0
Infections and infestations       
Upper Respiratory Infection * [4]  3/41 (7.32%)  3 0/55 (0.00%)  0 0/62 (0.00%)  0
sinusitis * [5]  4/41 (9.76%)  4 0/55 (0.00%)  0 0/62 (0.00%)  0
oral candidiasis * [6]  2/41 (4.88%)  2 0/55 (0.00%)  0 0/62 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Musculoskeletal pain * [7]  2/41 (4.88%)  2 0/55 (0.00%)  0 0/62 (0.00%)  0
Nervous system disorders       
insomnia * [8]  4/41 (9.76%)  4 0/55 (0.00%)  0 0/62 (0.00%)  0
Renal and urinary disorders       
urinary tract infection * [9]  2/41 (4.88%)  2 0/55 (0.00%)  0 0/62 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
[1]
2 reports of cushinoid face which could be related to steroid therapy in study. However other steroids had been used.
[2]
There were eight reports of abdominal discomfort, abdominal distress, non specific abdominal pains only one of which was later found to be in a patient positive for H pylori. All conditions improved without sequelae
[3]
two reports of seasonal allergies which would be expected in these patients
[4]
3 total upper respiratory infections reported. Maximum severity was moderate. All resolved without sequelae.
[5]
4 reports of sinusitis. Maximum severity was moderate. All resolved without sequelae.
[6]
2 cases of oral candidiasis which may have been related to steroid therapy in protocol. Both resolved with treatment
[7]
reports of back and hip pain, non specific, unlikely to be due to lupus or the study protocol.
[8]
4 reports of insomnia which could be related to steroid therapy in protocol. None were clinically significant
[9]
There were 2 reports of UTI. Both resolved without sequelae.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Joan T Merrill, M.D
Organization: Oklahoma Medical Research Foundation
Phone: 405-271-7805
Responsible Party: Joan Merrill, MD, Oklahoma Medical Research Foundation
ClinicalTrials.gov Identifier: NCT00987831     History of Changes
Other Study ID Numbers: OMRF 09-02
Pfizer Inc ( Other Grant/Funding Number: Pfizer investigator initiated study )
First Submitted: September 30, 2009
First Posted: October 1, 2009
Results First Submitted: August 28, 2013
Results First Posted: October 20, 2014
Last Update Posted: October 20, 2014