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Trial record 2 of 4 for:    enbrel | Recruiting, Not yet recruiting Studies | Ankylosing Spondylitis

Therapeutic Response to Tumor Necrosis Factor-alpha (TNF-alpha) Antagonists in Rheumatoid Arthritis. (TNF-alpha)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05379049
Recruitment Status : Recruiting
First Posted : May 18, 2022
Last Update Posted : May 18, 2022
Sponsor:
Information provided by (Responsible Party):
Hiwa Khidhir Saaed, University of Sulaimani

Brief Summary:

Rheumatoid arthritis (RA) is an autoimmune, chronic inflammatory disease and TNF-alpha has been recognized as a triggering cytokine in the induction of joints inflammation and is involved in the pathogenesis of RA.

Treatment for RA aims to reduce disease activity, prevent or manage joint deterioration and lower the risk of major comorbidities such as heart disease and stroke.

The strategy of targeting cytokines has significantly increased RA patient outcomes. Therefore management with biological disease-modifying antirheumatic drugs "bDMARD" (Etanercept, Infliximab, Adalimumab) should be considered, If the treatment goal is not met with the first conventional synthetic drug modifying antirheumatic drugs (csDMARD) strategy, or if there are poor prognostic factors.

The multi-biomarker disease activity test could be used to help standardise individual treatment decisions, especially in patients who failed to respond well to the traditional treatment.

Iraq does not currently have specific guidelines, which might pose a risk to patients' safety. More data about the choice of bDMARD is needed in terms of tracking therapeutic response, or whether TNF or other pro-inflammatory cytokines like interleukin-6 (IL-6) is the main factor for the development and severity of RA.

These data are important to improve the overall status of the patient, better choice of treatment and biomarkers to detect.

There is limited information on the treatment patterns of rheumatoid arthritis (RA) across Iraq including the Kurdistan Region. Therefore, the aim of this research is to evaluate the efficacy, and clinical responses of RA patients who have been treated with different anti-TNF, as well as on answering the research hypothesis, Can plasma TNF-alpha and IL-6 be used as markers of therapeutic response to TNF alpha antagonist in patients with RA?


Condition or disease Intervention/treatment
Rheumatoid Arthritis Inflammatory Arthritis Ankylosing Spondylitis Biological: Infliximab: Adalimumab; Etanercept;

Detailed Description:

Rheumatologists in Iraq, including those in the Kurdistan Region, rely on the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) guidelines and publications due to a lack of evidence-based national guidelines.

Several studies found that targeting TNF-alpha in the early stages of RA and evaluating serum TNF- levels, in combination with DAS28's assessment of disease clinical activity to track disease progression could result be advantageous for patients on anti-TNF medication in the future.

Objectives: The current research focuses on identifying the efficacy of three TNF-alpha antagonists (Etanercept, Infliximab, and Adalimumab) used currently in Sulaymaniyah Hospitals.

Methodology, an observational open-label study of ~60-80 adult patients with active RA from both genders that are registered at Rehabilitation and Rheumatology Center in Sulaymaniyah City who have been treated with biological agents (Etanercept, Infliximab, Adalimumab), regardless of disease activity and concomitant treatments.

Baseline data will be collected during the first visit and patients will be followed up during the study at regular intervals.

The study includes data of patients after filling the patient consent form, and are willingly giving their demographic data such as; Age, Sex, and Race (ethnic group). and answer the questions of multidimensional health assessment. Also measuring patients' weight at each visit, The clinical assessment of the patients is based on DAS28 (Disease Activity Score) by using ESR(Erythrocyte Sedimentation Rate), and VAS (Visual analogue score).

The laboratory data or the biomarkers at each visit include; CBC (complete blood count), C-reactive protein and ESR as inflammatory biomarkers, and detecting TNF-alpha and IL-6 to indicate the efficacy of the treatment and better choice of the treatment.

As for the statistical analysis plan, the Software SPSS (version 27) will be used.

Demographic and nominal results will be reported in percentages and frequencies.

Numerical results will be reported as the mean and standard deviation in cases of normal distribution, and as the median and interquartile range (IQR) in cases of skewed distribution.

The continuous variables CRP, TNF, IL-6 and the change over time, will be analyzed using linear mixed models for repeated measures. The chi-squared test will be used for dichotomous variables.

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Study Type : Observational
Estimated Enrollment : 80 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Evaluation of the Therapeutic Response to TNF-alpha Antagonist (Etanercept, Infliximab, Adalimumab) in Patients With Rheumatoid Arthritis; Using Plasma TNF-alpha as a Competent Biomarker. Single Center Study in Sulaymaniyah/ Iraq
Actual Study Start Date : March 1, 2022
Estimated Primary Completion Date : August 31, 2022
Estimated Study Completion Date : October 1, 2022



Intervention Details:
  • Biological: Infliximab: Adalimumab; Etanercept;
    Therapeutic drug monitoring, evaluation of clinical outcomes and laboratory analysis of biomarkers
    Other Name: Remicade, Remsima، Humira, amgevita، Enbrel


Primary Outcome Measures :
  1. Comparison of Plasma Tumor Necrosis Factor alpha (TNF-α) among different TNF alpha antagonist Therapy in Patients with Rheumatoid Arthritis. [ Time Frame: Up to 12 Weeks ]
    Tumor Necrosis Factor alpha (TNF-α) is a pro-inflammatory cytokine produced by activating macrophages and T-cells that play a key role in the production of other cytokines and the induction of chronic inflammation.

  2. Comparison of Plasma Interleukin-6 (IL-6) among different TNF alpha antagonist Therapy in Patients with Rheumatoid Arthritis. [ Time Frame: Up to 12 Weeks ]
    Interleukin-6 (IL-6) is a major pro-inflammatory cytokine, triggers the vicious circle of escalating RA disease activity via inducing immune activation and inflammation in RA.

  3. Mean change of C-reactive Protein (CRP) among different TNF alpha antagonist Therapy in Patients with Rheumatoid Arthritis. [ Time Frame: Up to 12 Weeks ]
    C-reactive protein (CRP) a potential marker of systemic inflammation and is elevated in patients with rheumatoid arthritis (RA).

  4. Mean change of Erythrocyte Sedimentation Rate (ESR) among different TNF alpha antagonist Therapy in Patients with Rheumatoid Arthritis. [ Time Frame: Up to 12 Weeks ]
    Erythrocyte sedimentation rate (ESR) is a popular hematology test that may detect and track an increase in inflammatory activity in the body, which can be caused by autoimmune illness, infections, or malignancies.

  5. Complete blood count (CBC) [ Time Frame: Up to 12 Weeks ]
    A complete blood count (CBC) is a blood test used to evaluate overall health and detect a wide range of hematological disorders, including anemia.

  6. Assessment of Disease Activity Score (DAS) [ Time Frame: Up to 12 weeks ]
    Disease Activity Score (DAS) is a continuous measure of RA disease activity that combines information from swollen joints, tender joints, acute phase response and general health.

  7. Assessment of Visual Activity Score (VAS) [ Time Frame: Up to 12 weeks ]
    Visual Activity Score (VAS) A psychometric pain rating scale for parameters that range across a continuum of values, such as pain. The VAS pain scale ranges from "no pain" to "worst pain," and patients mark a line to indicate how they are feeling.


Secondary Outcome Measures :
  1. A correlation between plasma Tumor Necrosis Factor alpha (TNF-α) and disease activity and severity. [ Time Frame: Up to 12 weeks ]
    To determine how different Tumor Necrosis Factor-alpha (TNF-α) antagonist medications affected plasma (TNF-α) levels and the Disease Activity Score (DAS) in rheumatoid arthritis (RA) patients.

  2. A correlation between plasma Interleukin-6 (IL-6) and disease activity and severity. [ Time Frame: Up to 12 weeks ]
    To determine how different Tumor Necrosis Factor-alpha (TNF-α) antagonist medications affected plasma Interleukin-6 (IL-6) levels and the Disease Activity Score (DAS) in rheumatoid arthritis (RA) patients.


Biospecimen Retention:   Samples Without DNA

Human Blood:

CBC (complete blood count), C-reactive protein and ESR as inflammatory biomarkers, and detecting TNF-alpha and IL-6



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
~60-80 adult patients [≥18 years] with Rheumatoid Arthritis from both genders registered at Rehabilitation and Rheumatology Center in Sulaymaniyah City, who are not responding to conventional DMARDs regardless of disease activity and concomitant treatments.
Criteria

Inclusion Criteria:

  • Meeting the ACR/EULAR 2010 criteria for rheumatoid arthritis (RA).
  • Patients (or Legal Guardian, if applicable) who are willing to give informed consent for the study period-time follow up.
  • Concomitant DMARDs
  • Duration of treatment with TNF-alpha antagonists <1 year, 1-5 years, >5 years

Exclusion Criteria:

  • Tubercle Bacillus (TB)
  • Hepatitis B, Hepatitis C
  • Pregnancy and lactation
  • Patients with heart failure.
  • Previous or concurrent malignancies

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05379049


Contacts
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Contact: Hiwa K Saaed, PhD +9647701530462 hiwa.saaed@univsul.edu.iq
Contact: Sana M Mohammed, BSc +9647702105174 sana.mohammed@univsul.edu.iq

Locations
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Iraq
Hiwa Khidhir Saaed Recruiting
Sulaymaniyah, Kurdistan Region, Iraq, 46001
Contact: Hiwa Saaed, PhD    07701530462    hiwa.saaed@univsul.edu.iq   
Contact: Sana M Mohammed, BSc    +9647702105174    sana.mohammed@univsul.edu.iq   
Sponsors and Collaborators
University of Sulaimani
Investigators
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Principal Investigator: Hiwa Saaed, PhD University of Sulaimani College of Pharmacy
Principal Investigator: Sana M Mohammed, BSc Directorate of Health, Sulaymaniyah
Publications:
Smolen JS, Landewe RBM, Bijlsma JWJ, Burmester GR, Dougados M, Kerschbaumer A, McInnes IB, Sepriano A, van Vollenhoven RF, de Wit M, Aletaha D, Aringer M, Askling J, Balsa A, Boers M, den Broeder AA, Buch MH, Buttgereit F, Caporali R, Cardiel MH, De Cock D, Codreanu C, Cutolo M, Edwards CJ, van Eijk-Hustings Y, Emery P, Finckh A, Gossec L, Gottenberg JE, Hetland ML, Huizinga TWJ, Koloumas M, Li Z, Mariette X, Muller-Ladner U, Mysler EF, da Silva JAP, Poor G, Pope JE, Rubbert-Roth A, Ruyssen-Witrand A, Saag KG, Strangfeld A, Takeuchi T, Voshaar M, Westhovens R, van der Heijde D. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020 Jun;79(6):685-699. doi: 10.1136/annrheumdis-2019-216655. Epub 2020 Jan 22.

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Responsible Party: Hiwa Khidhir Saaed, Lecturer and researcher at Department of Pharmacology & Toxicology, College of Pharmacy, University of Sulaimani
ClinicalTrials.gov Identifier: NCT05379049    
Other Study ID Numbers: UoS
First Posted: May 18, 2022    Key Record Dates
Last Update Posted: May 18, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: The data will be presented as a Mean of the sample population.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Hiwa Khidhir Saaed, University of Sulaimani:
Rheumatoid Arthritis, Cytokines
Additional relevant MeSH terms:
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Spondylitis
Spondylitis, Ankylosing
Spondylarthritis
Axial Spondyloarthritis
Etanercept
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Bone Diseases, Infectious
Infections
Bone Diseases
Spinal Diseases
Spondylarthropathies
Ankylosis
Adalimumab
Infliximab
Tumor Necrosis Factor Inhibitors
Anti-Inflammatory Agents
Antirheumatic Agents
Dermatologic Agents
Gastrointestinal Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents