Re-evaluation of Some Old Rheumatoid Arthritis Therapy: A Randomized Controlled Trial

NCT03194204 | Completed

• 1 other identifier: 17200080
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

Rheumatoid Arthritis (RA) is a chronic inflammatory disease characterized by joint swelling, joint tenderness and destruction of synovial joints, leading to severe disability and premature mortality.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (2)

• efficacy of doxycycline

  percentage of patients achieving remission or low disease activity as assessed by DAS28

  3 months after therapy

• safety of doxycycline in combination with MTX

  side effects

  at day one of the study and every months till the end of the study

Secondary Outcomes (2)

• CIMT as a method for detection of subclinical atherosclerosis in RA patients

  1 day

• MMP-3 and 9 as predictors of cardiovascular affection, disease activity and treatment response

  day 1 and 3 months follow up

Study Arms (2)

RA patients treated with methotrexate

ACTIVE COMPARATOR

Disease activity score(DAS28) matrix metalloproteinase-3(MMP-3) and matrix metalloproteinase-9(MMP-9), Erythrocyte sedimentation rate C- reactive protein Complete blood count Urine analysis Renal and liver function tests Lipid profile, blood glucose level Serum uric acid Rheumatoid factor (RF IgM, U/L) Anti- cyclic citrullinated peptide . Radiological assessment :Plain radiographs of both hands and feet in the postero-anterior views . Cardiac assessment :By electrocardiogram ( ECG ) and echocardiography , Carotid artery intima-medial thickness (IMT) will be done by colored doppler ultrasound.

Drug: Doxycycline Tablets

RA patients treated with methotrexate plus doxycycline

ACTIVE COMPARATOR

Disease activity score(DAS28) Matrix Metalloproteinase-3 (MMP-3) and Matrix Metalloproteinase-9 (MMP-9) Erythrocyte sedimentation rate C- reactive protein Complete blood count Urine analysis Renal and liver function tests Lipid profile, blood glucose level Serum uric acid , Rheumatoid factor (RF IgM(immunoglobulin M), U/L) Anti- cyclic citrullinated peptide. Radiological assessment :Plain radiographs of both hands and feet in the postero-anterior views. Cardiac assessment : By electrocardiogram ( ECG ) and echocardiography Carotid artery intima-medial thickness (IMT) will be done by colored doppler ultrasound.

Drug: Doxycycline Tablets

Interventions

Doxycycline Tablets DRUG

MMP-3 and MMP-9 will be done with blood samples using ELISA technique CIMT will be done using colored doppler ultrasound

Also known as: Erythrocyte sedimentation rate (ESR), Complete blood count (CBC)., Lipid profile, Renal and liver function tests, Serum uric acid, Rheumatoid factor (RF IgM, U/L), Anti- cyclic citrullinated peptide, plain radiographs of both hands and feet, electrocardiogram ( ECG ) and echocardiography, Carotid artery intima-medial thickness (CIMT), C-reactive protein (CRP), blood glucose level, Disease activity score(DAS28), Matrix metalloproteinase 3 and 9 (MMP-3)(MMP-9)

RA patients treated with methotrexate; RA patients treated with methotrexate plus doxycycline

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Patients included in this study are patients with RA (either newly or previously diagnosed) with their age between 18-50 years old having the same normal range of body mass index

You may not qualify if:

• \- The investigators will exclude patients with risk factors for atherosclerosis other than rheumatoid arthritis such as:
• Smoking.
• Obesity.
• Hypertension.
• Diabetes.
• History of renal or liver diseases.
• Corticosteroid therapy. 2- Intercurrent infections as they may interfere with levels of metalloproteinases.
• Pregnant or lactating females .

Sponsors & Collaborators

• Assiut University: lead

Study Sites (1)

Assiut University

Asyut, 71000515, Egypt

Location

Related Publications (11)

• Abdelnaseer M, Elfayomi N, Esmail EH, Kamal MM, Hamdy A, Samie RMA, Elsawy E. Relationship between matrix metalloproteinase-9 and common carotid artery intima media thickness. Neurol Sci. 2016 Jan;37(1):117-122. doi: 10.1007/s10072-015-2358-z. Epub 2015 Aug 30.

  PMID: 26319043 RESULT

• Grzela K, Litwiniuk M, Zagorska W, Grzela T. Airway Remodeling in Chronic Obstructive Pulmonary Disease and Asthma: the Role of Matrix Metalloproteinase-9. Arch Immunol Ther Exp (Warsz). 2016 Feb;64(1):47-55. doi: 10.1007/s00005-015-0345-y. Epub 2015 Jun 28.

  PMID: 26123447 RESULT

• Ma JD, Zhou JJ, Zheng DH, Chen LF, Mo YQ, Wei XN, Yang LJ, Dai L. Serum matrix metalloproteinase-3 as a noninvasive biomarker of histological synovitis for diagnosis of rheumatoid arthritis. Mediators Inflamm. 2014;2014:179284. doi: 10.1155/2014/179284. Epub 2014 Jul 23.

  PMID: 25147433 RESULT

• Mittal B, Mishra A, Srivastava A, Kumar S, Garg N. Matrix metalloproteinases in coronary artery disease. Adv Clin Chem. 2014;64:1-72. doi: 10.1016/b978-0-12-800263-6.00001-x.

  PMID: 24938016 RESULT

• Everett BM, Pradhan AD, Solomon DH, Paynter N, Macfadyen J, Zaharris E, Gupta M, Clearfield M, Libby P, Hasan AA, Glynn RJ, Ridker PM. Rationale and design of the Cardiovascular Inflammation Reduction Trial: a test of the inflammatory hypothesis of atherothrombosis. Am Heart J. 2013 Aug;166(2):199-207.e15. doi: 10.1016/j.ahj.2013.03.018. Epub 2013 May 3.

  PMID: 23895801 RESULT

• Bernetti M, Abbate R, Cerini G, Gensini GF, Poggesi L, Boddi M. [Carotid and femoral intima-media thickness as an early atherosclerotic marker. Advantages and limits]. G Ital Cardiol (Rome). 2011 Jan;12(1):72-81. Italian.

  PMID: 21428031 RESULT

• Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Menard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovsky J, Wolfe F, Hawker G. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010 Sep;62(9):2569-81. doi: 10.1002/art.27584.

  PMID: 20872595 RESULT

• Webster G, Del Rosso JQ. Anti-inflammatory activity of tetracyclines. Dermatol Clin. 2007 Apr;25(2):133-5, v. doi: 10.1016/j.det.2007.01.012.

  PMID: 17430750 RESULT

• Nakashima Y, Chen YX, Kinukawa N, Sueishi K. Distributions of diffuse intimal thickening in human arteries: preferential expression in atherosclerosis-prone arteries from an early age. Virchows Arch. 2002 Sep;441(3):279-88. doi: 10.1007/s00428-002-0605-1. Epub 2002 Mar 14.

  PMID: 12242525 RESULT

• del Rincon ID, Williams K, Stern MP, Freeman GL, Escalante A. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum. 2001 Dec;44(12):2737-45. doi: 10.1002/1529-0131(200112)44:123.0.CO;2-%23.

  PMID: 11762933 RESULT

• Ibrahem EM, El-Gendi SS, Mahmoud AA, Abdel-Aal SM, El Nouby FH, El-Deen Mohammed HS. Predictors of Cardiovascular Affection in Patients with Active Rheumatoid Arthritis: Secondary Analysis of a Randomized Controlled Trial. Curr Rheumatol Rev. 2021;17(2):258-266. doi: 10.2174/1573397116666201113090145.

  PMID: 33185166 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Doxycycline; Blood Sedimentation; Blood Cell Count; Rheumatoid Factor; epicatechin gallate; C-Reactive Protein; Blood Glucose; Matrix Metalloproteinase 3

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Hematologic Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cell Count; Cytological Techniques; Cell Physiological Phenomena; Blood Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Autoantibodies; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Albumins; Acute-Phase Proteins; Glucose; Hexoses; Monosaccharides; Sugars; Carbohydrates; Matrix Metalloproteinases, Secreted; Matrix Metalloproteinases; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Intercellular Signaling Peptides and Proteins

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: principal investigator

Model Details: A group of patients will receive methotrexate only, another group will receive methotrexate plus doxycycline

Study Record Dates

• First Submitted: June 10, 2017
• First Posted: June 21, 2017
• Study Start: October 1, 2019
• Primary Completion: February 20, 2020
• Study Completion: February 20, 2020
• Last Updated: May 18, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)