Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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:
Information provided by (Responsible Party):
Gaylis, Norman B., M.D.

Tracking Information
First Submitted Date  ICMJE September 9, 2013
First Posted Date  ICMJE September 23, 2013
Results First Submitted Date  ICMJE May 23, 2018
Results First Posted Date  ICMJE January 18, 2019
Last Update Posted Date January 18, 2019
Study Start Date  ICMJE September 2013
Actual Primary Completion Date September 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 17, 2019)
Change From Baseline in Clinical Disease Activity Index (CDAI) Score [ Time Frame: Baseline, Month 3 and Month 6 ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 18, 2013)
Clinical Disease Activity Index (CDAI) score Evaluation [ Time Frame: Baseline, Month 3 and Month 6 ]
The primary objective would be to evaluate the effect of the utilization of two 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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 17, 2019)
  • Evaluation of MRI Structural Improvements [ Time Frame: Baseline, 3 months, 6 months ]
    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)
  • Number of Participants With Increased or Decreased Erosions of the Hand and Wrist [ Time Frame: Month 3 and Month 6 ]
    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).
  • Comparison of Clinical Disease Activity Index (CDAI) Scores to Positive Magnetic Resonance Imaging (MRI) Findings [ Time Frame: Month 6 ]
    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
Original Secondary Outcome Measures  ICMJE
 (submitted: September 18, 2013)
  • Evaluation of MRI Structural Improvements [ Time Frame: 3 months, 6 months ]
    To measure and record the change from baseline in the presence of synovitis and bone edema at months 3 and 6
  • Change from baseline in erosions as measured by Magnetic Resonance Imaging (MRI) [ Time Frame: Month 3, Month 6 ]
    Comparison of the change in erosion scores as measured by Magnetic Resonance Imaging (MRI) findings
  • Number of patients at months 3 and 6 without new bone erosions and/or joint space narrowing on MRI and X-ray [ Time Frame: Month 3 and Month 6 ]
    Record the number of patients without new bone erosions and/or joint space narrowing as measured on Magnetic Resonance Imaging (MRI) and X-ray
  • Measurement of the number of patients who reach American College of Rheumatology (ACR) remission at defined levels (20%, 50%, 70%) [ Time Frame: Month 3 and Month 6 ]
    Calculate the number of patients who reach American College of Rheumatology (ACR)remission of 20%, 50% and 70% using the ACR scoring system
  • Comparison of Clinical Disease Activity Index (CDAI) Scores to Positive Magnetic Resonance Imaging (MRI) Findings [ Time Frame: Baseline, Month 3 and Month 6 ]
    Comparison of the clinical findings as measured by the Clinical Disease Activity Index (CDAI) versus the positive structural findings as measured by Magnetic Resonance Imaging (MRI)
  • Correlation of changes in Magnetic Resonance Imaging (MRI) scores with changes in van der Heijde Sharp(VdH Sharp)X-ray scores [ Time Frame: Month 3 and Month 6 ]
    Correlation of the changes in the Magnetic Resonance Imaging (MRI) scoring versus the X-ray scoring system
  • Comparison of the clinical laboratory results with the positive Magnetic Resonance Imaging (MRI) findings [ Time Frame: Baseline, Month 3 and Month 6 ]
    Comparison of the clinical laboratory test results of Rheumatoid Factor (RF), anti-citrullinated protein antibody (anti-CCP antibody), C-reactive protein (CRP), and sedimentation rate (ESR)versus the positive structural findings on Magnetic Resonance Imaging (MRI)
Current Other Pre-specified Outcome Measures
 (submitted: January 17, 2019)
Participants With Increased and Decreased C-Reactive Protein (CRP) Values and Erythrocyte Sedimentation Rates (ESR) [ Time Frame: Month 6 ]
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.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Effect of Corticotrophin (ACTH) in Combination With Methotrexate in Newly Diagnosed Rheumatoid Arthritis Patients
Official Title  ICMJE Study of The Effect of Corticotrophin in Combination With Methotrexate in Newly Diagnosed Rheumatoid Arthritis Patients From a Clinical and Structural Perspective As Measured by a Clinical Disease Activity Index Score and Bone Edema, Synovitis and Erosions on Magnetic Resonance Imaging
Brief Summary The purpose of the study is to evaluate the effect of the utilization of two 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 well as the structural findings on Magnetic Resonance Imaging (MRI). Corticotrophin (ACTH) may prevent the well documented structural progression damage in RA patients using disease-modifying antirheumatic drug (DMARD) therapy alone.
Detailed Description This is a Phase II 24-week open-label study to evaluate the efficacy and safety of H.P. Acthar Gel Respository Injection, Corticotrophin( ACTH) administered to newly diagnosed patients with rheumatoid arthritis in conjunction with methotrexate, folllowed by a 24 week follow-up period. There will be a total of twenty (20) patients and two (2) treatment groups with 10 patients in each treatment group
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Rheumatoid Arthritis
Intervention  ICMJE Drug: 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
Other Name: Acthar, Corticotrophin, ACTH
Study Arms  ICMJE
  • Active Comparator: corticotrophin 80 units
    Ten (10) patients will receive 80 units of corticotrophin Subcutaneous (SC) weekly
    Intervention: Drug: corticotrophin 80 units
  • Active Comparator: corticotrophin 80 units twice a week
    Ten (10) patients will receive 80 units of corticotrophin Subcutaneous (SC) twice a week
    Intervention: Drug: corticotrophin 80 units
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 18, 2013)
20
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE September 2016
Actual Primary Completion Date September 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patient must be at least 18 years old at the screening visit.
  2. Patient must be able to understand the information provided to them and to give written Informed Consent.
  3. Female patients must be either postmenopausal for at least 1 year, surgically incapable of childbearing, or effectively practicing an acceptable method of contraception (oral/parenteral/implantable hormonal contraceptives, Intrauterine Device (IUD), or barrier and spermicide). Abstinence only is not an acceptable method. Patients must agree to use adequate contraception during the study and for 4 weeks after their last dose of corticotrophin (ACTH). Male patients must agree to ensure they or their female partner(s) are using adequate contraception during the study and for 4 weeks after the patient receives their last dose of corticotrophin (ACTH).
  4. Patients must have a new diagnosis of adult-onset rheumatoid arthritis (RA) as defined by the 2010 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria and who have had symptoms for <1 year.
  5. Patients must be experiencing mild to moderate rheumatoid arthritis ( RA), have at least 6 tender and 6 swollen joints at screening and a clinical disease activity index (CDAI) score of > 6.0
  6. A Baseline Magnetic Resonance Imaging ( MRI) must show the presence of osteitis or erosions in the hand or wrist.
  7. Patients must be able and willing to comply with the requirements of the study protocol.
  8. Patients must have a C-reactive Protein (CRP) or erythrocyte sedimentation rate (ESR) > upper limits of normal

Exclusion criteria:

  1. Patients who have a diagnosis of any other inflammatory arthritis (e.g., psoriatic arthritis or ankylosing spondylitis).
  2. Patients with exposure to any disease modifying antirheumatic drug (DMARD), Biologic, Non-biologic or experimental medication for the treatment of rheumatoid arthritis (RA).
  3. Patients with a non-inflammatory type of arthritis (e.g. osteoarthritis or fibromyalgia) that in the Investigator's opinion is symptomatic enough to interfere with evaluation of the effect of study drug on the patient's primary diagnosis of rheumatoid arthritis (RA).
  4. Patients with history of an infected joint prosthesis at any time with that prosthesis still in situ.
  5. Patients have received prohibited medication:

    • non-steroidal anti-inflammatory drug (NSAIDs /COX-2 inhibitors) (any change in dose regimen in the 7 days prior to baseline)
    • Oral corticosteroids within 4 weeks of baseline
    • Intra-muscular, intra-venous, intra-articular (IM/IV/IA) corticosteroids/ Intra-articular (IA) Hyaluronic acid (any dose 28 days prior to baseline)
  6. Female patients who are breast-feeding, pregnant, or plan to become pregnant during the trial or within twelve weeks following last dose of study drug.
  7. Patients with a history of chronic infection due to fungal, parasitic or mycotic pathogens during the preceding year, recent serious or life-threatening infection within 6 months (including herpes zoster), or any current sign or symptom that may indicate an infection.
  8. Patients with active Tuberculosis (TB) (or history of active TB), positive chest X-ray for TB, or positive (defined as induration of ≥ 5mm) purified protein derivative (PPD) skin test, positive QuantiFERON, or patients having close contact with an individual with active TB. Patients having a PPD skin test ≥ 5 mm or a positive QuantiFERON test can enter the study, provided that active TB is excluded and provided that they are adequately treated for latent TB (e.g., isonicotinic acid hydrazide [INH therapy] for 9 months [with vitamin B6]) and provided that appropriate treatment is initiated simultaneously with the first administration of ACTH.
  9. Patients at a high risk of infection (e.g. leg ulcers, indwelling urinary catheter and persistent or recurrent chest infections and patients who are permanently bedridden or wheelchair bound).
  10. Patients with a known allergy or intolerance to steroids 11 Concurrent malignancy or a history of malignancy (other than carcinoma of the cervix or basal cell carcinoma successfully treated more than 5 years prior to screening).

12. Patients with a current or recent history of severe, progressive, and/or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological or cerebral disease.

13. Patients with class III or IV congestive heart failure according to the New York Heart Association (NYHA) 1964 classification criteria.

14. Patients with a history of, or suspected, demyelinating disease of the central nervous system (e.g. multiple sclerosis or optic neuritis).

15. Patients with any other condition (e.g. clinically significant laboratory values) which in the Investigator's judgment would make the patient unsuitable for inclusion in the study.

16. Patients who have a metal device affected by MRI (e.g., any type of electronic, mechanical, or magnetic implant; cardiac pacemaker; aneurysm clip(s); implanted cardioverter defibrillator; or a cochlear implant) 17. Patients who have a potential ferromagnetic foreign body (metal slivers, metal shavings, other metal objects) for which they have sought medical attention.

18. Concurrent steroid use for any concomitant disease. 19. Subjects who are known to be Human Immunodeficiency Virus (HIV), Hepatitis B or Hepatitis C positive

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01948388
Other Study ID Numbers  ICMJE RA2013-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Gaylis, Norman B., M.D.
Study Sponsor  ICMJE Gaylis, Norman B., M.D.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Norman B Gaylis, MD AARDS Research, Inc.
PRS Account Gaylis, Norman B., M.D.
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP