Venlafaxine as Adjunct Therapy in Rheumatoid Arthritis

Official title

The Effect of Venlafaxine as an Adjunct Therapy on The Clinical Outcome of Rheumatoid Arthritis Patients

Overview

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation of the joints, leading to pain, swelling, disability, and reduced quality of life. Current therapies, although effective, may have limited efficacy or tolerability in some patients. Biological DMARDs are often associated with adverse effects, including increased risk of serious infections and heart failure. Long-term use may also increase the risk of malignancies. These limitations, together with their high cost. Venlafaxine, a serotonin-norepinephrine reuptake inhibitor (SNRI), has shown potential anti-inflammatory properties in addition to its antidepressant effects. This study aims to evaluate the efficacy and safety of venlafaxine as an adjunct therapy in the management of rheumatoid arthritis.

Detailed description

Eligible patients will be randomly assigned using block randomization to one of the following groups:

Venlafaxine group: 35 patients will receive the standard RA treatment in addition to venlafaxine extended-release (XR) initiated at a dose of 75 mg/day for one week to ensure tolerability, followed by an increase to 150 mg/day, which will be maintained for the duration of the study (12 weeks) The control group: 35 patients will receive the standard treatment of RA, which will be maintained for the duration of the study (12 weeks).

At baseline the following data will be collected from the patient :

Age - Gender- Body mass index (BMI) - Medical history- Medication history- Smoking status- Disease duration- Dose of corticosteroids if present.

Efficacy evaluation Serum CRP and ESR will be assessed at baseline and after 3 months using routine analysis

• Disease activity using DAS-28-CRP Disease severity will be assessed using DAS-28-CRP at baseline and after 3 months Safety assessment All patients will be assessed on a monthly basis during clinic visits and on a weekly basis during phone calls to assess the adverse effects of venlafaxine. All patients will be educated about the study protocol and will be required to report the occurrence of any of them.

Serum biomarker A blood ample will be withdrawn from each patient at baseline and after 3 month and the separated sera will be stored at -80o C till analysis. These sera will be used to assess the level of VEGF using commercial ELISA kits.

Quality of life assessment using health assessment questionnaire (HAQ-DI)

Interventions

• Drug venlafaxine extended-release (XR)
  35 patients will receive the standard RA treatment in addition to venlafaxine extended-release (XR) initiated at a dose of 75 mg/day for one week to ensure tolerability, followed by an increase to 150 mg/day, which will be maintained for the duration of the study (12 weeks)
• Other Standard conventional Rheumatoid Arthritis Therapy
  35 patients will receive the standard treatment of RA, which will be maintained for the duration of the study (12 weeks).

Primary outcome measures

• Change in Disease Activity Score 28 (DAS28-CRP) [Time frame: Baseline and 3 months]

Secondary outcome measures (5)

• Change in C-reactive protein (CRP) [Time frame: Baseline and 3 months]
• Change in erythrocyte sedimentation rate (ESR) [Time frame: Baseline and 3 months]
• Change in serum vascular endothelial growth factor (VEGF) [Time frame: at baseline and after 3 months.]
• safety and tolerability of venlafaxine [Time frame: at baseline and after 3 months.]
• Health assessment questionnaire HAQ-DI. [Time frame: at baseline and after 3 months.]

Eligibility criteria

Inclusion criteria

• Adult patients with definite RA according to ACR/ EULAR 2010 criteria.
• Patients on stable DMARDs+/- steroid regimen for at least 6 months.
• Patients with moderate to high disease activity (DAS28 ≥ 3.2) despite treatment

Exclusion criteria

• Patients receiving biologics or targeted DMARDs
• Known hypersensitivity to venlafaxine or any of its components.
• Concurrent Use of MAOIs
• Women who are pregnant or breastfeeding.
• Uncontrolled hypertension
• Unstable Heart Conditions
• Patients receiving any other anti-depressant
• Psychiatrically unstable patients as indicated by a history of psychosis or mania, current suicidal ideation, current substance abuse or dependence.
• Renal dysfunction (creatinine clearance <60 mL/min)
• Hepatic dysfunction (ALT and AST more than 3 times upper normal limits)
• Patients with active major bleeding or high risk of bleeding

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Arleevskaya, M., Takha, E., Petrov, S., Kazarian, G., Novikov, A., & Larionova, R. (2021). Causal risk and protective factors in rheumatoid arthritis : A genetic update. Journal of Translational Autoimmunity, 4, 100119. https://doi.org/10.1016/j.jtauto.2021.100119 BASSEL EL-ZORKANY, M.D., W. A. M. D. ., & LOBNA A. MAGED, M.D., N. E.-G. M. D. . M. (2023). Evaluation of Rheumatoid Arthritis Knowledg

Identifiers

NCT: NCT07497282 · REC # 407

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗