The Effect of Corticotrophin (ACTH) in Combination With Methotrexate in Newly Diagnosed Rheumatoid Arthritis Patients

• ClinicalTrials.gov Identifier: NCT01948388
• Recruitment Status: Completed
• First Posted: September 23, 2013
• Results First Posted: January 18, 2019
• Last Update Posted: January 18, 2019
• Sponsor: Gaylis, Norman B., M.D.
• Information provided by (Responsible Party): Gaylis, Norman B., M.D.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Rheumatoid Arthritis
• Intervention: Drug: corticotrophin 80 units
• Enrollment: 20

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Group 1	Group 2
Arm/Group Description	Ten (10) Patients were treated with 80 U of ACTH once weekly and MTX 12.5-25 mg/week for a period of 6 months. Eight (8) Patients completed the 6 month trial in this group	Ten (10) patients were treated with 80 U of ACTH twice a week and MTX 12.5-25 mg/week for a 6 month period. Nine (9) patients completed the trial in this group over the 6 month period.
Period Title: Overall Study
Started	10	10
Completed	8	9
Not Completed	2	1

Baseline Characteristics

Arm/Group Title		Corticotrophin 80 Units	Corticotrophin 80 Units Twice a Week	Total
Arm/Group Description		Ten (10) patients will receive 80 units of corticotrophin Subcutaneous (SC) weekly corticotrophin 80 units: Comparison of different dosages of the drug. Ten patients will receive 80 units of corticotrophin weekly. Ten patients will receive 80 units bi-weekly of corticotrophin	Ten (10) patients will receive 80 units of corticotrophin Subcutaneous (SC) twice a week corticotrophin 80 units: Comparison of different dosages of the drug. Ten patients will receive 80 units of corticotrophin weekly. Ten patients will receive 80 units bi-weekly of corticotrophin	Total of all reporting groups
Overall Number of Baseline Participants		10	10	20
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	10 participants	10 participants	20 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	7 70.0%	7 70.0%	14 70.0%
	>=65 years	3 30.0%	3 30.0%	6 30.0%
Age, Continuous; Mean (Full Range); Unit of measure: Years
	Number Analyzed	10 participants	10 participants	20 participants
		60; (49 to 77)	57; (36 to 78)	59; (36 to 78)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	10 participants	10 participants	20 participants
	Female	9 90.0%	10 100.0%	19 95.0%
	Male	1 10.0%	0 0.0%	1 5.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	10 participants	10 participants	20 participants
		10	10	20

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Clinical Disease Activity Index (CDAI) Score
Description	To evaluate the effect of the use of 2 doses of corticotrophin (ACTH) as a treatment in patients with early onset rheumatoid arthritis as an alternative to conventional steroid therapy by evaluating the change from baseline in the clinical findings as measured by Clinical Disease Activity Index (CDAI) scores. The CDAI is calculated at the specified time points using the formula: CDAI = SJC(28) + TJC(28) + PGA + EGA SJC(28): Swollen 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs including thumb IP, knees) Interpretation: A lower CDAI score from Baseline would mean improvement in disease activity and an increase in CDAI score from Baseline would mean an increase in disease activity or a worsening in disease activity. Scores: 0.0-2.8 = Range for Remission; 2.9-10.0 = Range for Low disease activity; 10.1-22.0 Range for Moderate disease activity; 22.1-76 Range for High disease activity.Total range is from 0-100, with the high scores representing high disease activity.
Time Frame	Baseline, Month 3 and Month 6

Outcome Measure Data

Analysis Population Description

Total number of Patients who complete 6 months of treatment in both groups doses weekly Group 1, and dosed twice a week Group 2

Arm/Group Title		Group 1	Group 2
Arm/Group Description:		Ten (10) Patients were treated with 80 U of ACTH once weekly and MTX 12.5-25 mg/week for a period of 6 months. Eight (8) Patients completed the 6 month trial in this group	Ten (10) patients were treated with 80 U of ACTH twice a week and MTX 12.5-25 mg/week for a 6 month period. Nine (9) patients completed the trial in this group over the 6 month period.
Overall Number of Participants Analyzed		9	8
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline	remission	0 0.0%	0 0.0%
	low disease activity	0 0.0%	0 0.0%
	moderate disease activity	0 0.0%	0 0.0%
	high disease activity	9 100.0%	8 100.0%
Month 3	remission	3 33.3%	1 12.5%
	low disease activity	2 22.2%	4 50.0%
	moderate disease activity	4 44.4%	2 25.0%
	high disease activity	0 0.0%	1 12.5%
Month 6	remission	2 22.2%	3 37.5%
	low disease activity	4 44.4%	3 37.5%
	moderate disease activity	2 22.2%	2 25.0%
	high disease activity	1 11.1%	0 0.0%

2. Secondary Outcome

Title	Evaluation of MRI Structural Improvements
Description	To compare the number of patients who have synovitis, oseitis and erosions at Baseline, Month 3 and Month 6. Normal range for synovitis, osteitis and erosions is zero (0)
Time Frame	Baseline, 3 months, 6 months

Outcome Measure Data

Analysis Population Description

Total number of Patients who complete 6 months of treatment in both groups doses weekly Group 1, and dosed twice a week Group 2

Arm/Group Title	Group 1	Group 2
Arm/Group Description:	Patients being weekly dosed with ACTH at 80 units	Patients receiving twice weekly doing of 80 units ACTH
Overall Number of Participants Analyzed	9	8
Measure Type: Number; Unit of Measure: participants
Baseline : synovitis	8	7
Baseline : osteitis	8	4
Baseline : erosions	9	8
Month 3 : synovitis	6	7
Month 3 : osteitis	6	6
Month 3 : erosions	9	8
Month 6 : synovitis	5	7
Month 6 : osteitis	4	4
Month 6 : erosions	7	8

3. Secondary Outcome

Title	Number of Participants With Increased or Decreased Erosions of the Hand and Wrist
Description	Comparison of the change in the number of erosions seen in the joints of the hand and wrist as measured by Magnetic Resonance Imaging (MRI) findings. Regression indicates improvement in the number of erosions seen from Baseline and Progression indicates worsening in the number of erosions seen from Baseline. Normal range is zero (0).
Time Frame	Month 3 and Month 6

Outcome Measure Data

Analysis Population Description

Total number of Patients with erosions who completed 6 months of treatment in both groups doses weekly Group 1, and dosed twice a week Group 2

Arm/Group Title	Group 1	Group 2
Arm/Group Description:	Patients being weekly dosed with ACTH at 80 units	Patients receiving twice weekly doing of 80 units ACTH
Overall Number of Participants Analyzed	9	8
Measure Type: Number; Unit of Measure: participants
Month 3 : Progressed erosions	1	3
Month 3 : Regressed erosions	0	2
Month 6 : Progressed erosions	2	2
Month 6 : Regressed erosions	1	2

4. Secondary Outcome

Title	Comparison of Clinical Disease Activity Index (CDAI) Scores to Positive Magnetic Resonance Imaging (MRI) Findings
Description	Comparison of the clinical findings as measured by the Clinical Disease Activity Index (CDAI) versus the structural findings as measured by Magnetic Resonance Imaging (MRI). Improvement is measured as a reduction in CDAI score from Baseline to Month 6 and improvement in MRI is regression of erosions, oseitis and synovitis at month 6. Norman MRI score is zero (0). CDAI: 0.0-2.8 remission; 2.9-10.0 low disease activity; 10.1-22 moderate disease activity; 22.1-76 high disease activity. A decrease in CDAI score is improvement
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

Total number of Patients who complete 6 months of treatment in both groups doses weekly Group 1, and dosed twice a week Group 2

Arm/Group Title	Group 1	Group 2
Arm/Group Description:	Patients being weekly dosed with ACTH at 80 units	Patients receiving twice weekly doing of 80 units ACTH
Overall Number of Participants Analyzed	9	8
Measure Type: Number; Unit of Measure: participants
# of patients whose CDAI score improved	8	8
# of patients whose overall MRI improved	6	5

5. Other Pre-specified Outcome

Title	Participants With Increased and Decreased C-Reactive Protein (CRP) Values and Erythrocyte Sedimentation Rates (ESR)
Description	comparisons not statistical analysis will be made from Baseline and Month 6 of the C- reactive Protein (CRP) values and Erythrocyte Sedimentation Rate (ESR) to determine the number of patients whose test result improved or worsenedCRP value (normal range <1.0 mg/dl). ESR (normal range 0-28 mm/hr) . If the value is increased, the disease activity worsened. If the value is reduced the disease activity is improved.
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

Total number of Patients who complete 6 months of treatment in both groups doses weekly Group 1, and dosed twice a week Group 2

Arm/Group Title		Group 1	Group 2
Arm/Group Description:		Patients being weekly dosed with ACTH at 80 units	Patients receiving twice weekly doing of 80 units ACTH
Overall Number of Participants Analyzed		9	8
Measure Type: Count of Participants; Unit of Measure: Participants
CRP Values	# of patient with Decreased values	8 88.9%	7 87.5%
	# of patients with Increased values	1 11.1%	1 12.5%
ESR Values	# of patient with Decreased values	9 100.0%	8 100.0%
	# of patients with Increased values	0 0.0%	0 0.0%

Adverse Events

Time Frame	all adverse events were collected from the date of signing Informed Consent and Discontinuation or Completion of the trial. There were no adverse events either serious or non-serious to be reported.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Group 1	Group 2
Arm/Group Description	Ten (10) Patients were treated with 80 U of ACTH once weekly and MTX 12.5-25 mg/week for a period of 6 months. Eight (8) Patients completed the 6 month trial in this group	Ten (10) patients were treated with 80 U of ACTH twice a week and MTX 12.5-25 mg/week for a 6 month period. Nine (9) patients completed the trial in this group over the 6 month period.
All-Cause Mortality
	Group 1	Group 2
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Group 1	Group 2
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/10 (0.00%)	0/10 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Group 1	Group 2
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/10 (0.00%)	0/10 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT 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: Joanne Sagliani
• Organization: Arthritis & Rheumatic Disease Specialties
• Phone: 3059324162
• EMail: drnbg@rheum-care.com

• Responsible Party: Gaylis, Norman B., M.D.
• ClinicalTrials.gov Identifier: NCT01948388
• Other Study ID Numbers: RA2013-01
• First Submitted: September 9, 2013
• First Posted: September 23, 2013
• Results First Submitted: May 23, 2018
• Results First Posted: January 18, 2019
• Last Update Posted: January 18, 2019