Rheumatoid ArthritisEarly Phase 1NCT06108518
Clinical Study Evaluating the Effect of Carvedilol in Patients With Active Rheumatoid Arthritis
A Early Phase 1 study testing Carvedilol in people with Rheumatoid Arthritis, run by Tanta University.
Trial summary
This study aims at investigating the possible efficacy and safety of carvedilol as an adjunctive therapy in patients with active rheumatoid arthritis and hypertension. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Carvedilol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- No sites listed yet
- Study dates
- 1 Jun 2024to Nov 2024
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Patients with active rheumatoid arthritis (not in remission) according to American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 criteria i.e 28 joints disease activity score (DAS-28) >2.6.
- Patients with hypertension who are candidate to carvidolol.
- Age range between 18 and 60 years old.
- The studywillbecarriedoutbetween June 2023 and June 2025.
- Both sexes.
- Sex ratio, body mass index (BMI), age, disease activity, and disease duration matched patients.
- Patients receive matched doses of standard treatment including methotrexate, non-steroidal anti-inflammatory drugs, selective cyclooxygenase-2 inhibitors, acetaminophen, and low dose of oral corticosteroids (prednisolone < 15 mg) will be allowed to be enrolled the trial.
- Intravenous, intra-articular or intramuscular corticosteroids; intra-articular hyaluronate sodium and biological DMARDs will not be permitted less than 4 weeks before the first dose of carvedilol.
Who cannot join
- Patients with congestive heart failure, other heart disease (arrhythmia, ischemic heart disease including angina and myocardial infarction).
- Patients with other inflammatory diseases and active infection.
- Patients with glaucoma.
- Patients with asthma, COPD, other lung diseases.
- Patients with hepatic and biliary diseases.
- Patients with chronic renal failure or those on dialysis.
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- Patients with peripheral intermittent claudication and peripheral circulatory disorders.
- Patients receiving oral pednisolone greater than 15 mg/day.
- Patients receiving biological DMARDs.
- Patients with hypersensitivity to carvedilol.
- Patients using antioxidants.
- Pregnant and lactating females.
- Patients receiving digitalis, anti-arrhythmic (amiodarone, propafenone) MAOI, cyclosporine, calcium channel blockers (verapamil, deltiazem), beta blockers, other antihypertensive medications hepatic microsomal enzymes inducers or inhibitors (phenytoin, rifampin, valoproate), oral hypoglycemic and insulin to avoid potential pharmacodynamics
Trial locations and contacts
No sites are listed yet.
Dr/Eman Ibrahim, Lecturer contact
About this study
This study aims at investigating the possible efficacy and safety of carvedilol as an adjunctive therapy in patients with active rheumatoid arthritis and hypertension.
Read the detailed description
heumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily affects the lining of the synovial joints and is associated with progressive disability, premature death, and socioeconomic burdens. It is characterized with chronic production of pro-inflammatory cytokines, which lead to cartilage and bone degradation that results in tissue destruction by the patients' immune system (Guo et al., 2018).
The high systemic inflammatory burden associated with RA appears to be a key driver of increased CV risk. This inflammatory state is linked to endothelial dysfunction and accelerated atherosclerosis (Giollo et al., 2018). Consequently, RA increases the risk of cardiovascular (CV) mortality by up to 50% compared with the general population and CV disease is the leading cause of death in RA patients. This leads to suggestion that reducing inflammation lowers CV risk in RA (Dijkshoorn et al., 2022).
Therapies targeting inflammation remain the mainstay of RA treatment such as non- steroidal anti-inflammatory drugs (NSAIDs), non-biologic and biologic disease-modifying anti-rheumatic drugs (DMARDs), immune-osuppressants, and corticosteroids. However, current treatment strategies have many adverse effects and a significant proportion of RA patients did not effectively respond to them (Aletaha and Smolen., 2018). Consequently, it is crucial to find new therapeutic approaches for the management of inflammation as well as the prevention of cardiovascular complications in rheumatoid arthritis patients.
Carvedilol is a non-selective β-blocker with α-adrenergic receptor antagonism properties which has been safely used in treatment of several cardiovascular disorders (Prajapati et al., 2017). Previous animal studies highlights evidences for the promising anti- arthritic effects of carvedilol that could be mediated through attenuation of leukocyte migration, alleviation of oxidative stress and suppression of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interlukin-6 (IL-6) and eicosanoids including prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) (Arab and El-Sawalhi, 2013; Ahmed et al., 2017; Osman et al., 2017).
Taken together, carvedilol has powerful antioxidant/anti-inflammatory properties; we aimed to investigate its protective potential against arthritis that may add further benefits for its clinical usefulness especially in RA patients with concomitant cardiovascular disorders
- Conditions
- Rheumatoid Arthritis
- Being tested
- Carvedilol
- Keywords
- Carvedilol, Hypertension
- Medical subject headings
- Arthritis, Rheumatoid, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarvedilolDrug
Treatment group will take carvedilol 12.5mg once a day for 2 days; this is increased to 25 mg once a day or 12.5 mg twice a day for 3 months.
| Study group | Role | What they receive |
|---|---|---|
| Control group | Placebo comparator | Group1 (Placebo group; n=35) which will receive the standard treatment for RA plus placebo tablet for 3 months. Receives: Drug: Carvedilol |
| Treatment group | Active comparator | Group 2 (Carvedilol group; n=35) which will receive the standard treatment for RA plus carvedilol 12.5mg once a day for 2 days; this is increased to 25 mg once a day or 12.5 mg twice a day for 3 months. Receives: Drug: Carvedilol |
What is being measured
The primary outcome is the main question the study is designed to answer.
change in DAS-28-CRP score and the Multidimensional Health Assessment Questionnaire (MDHAQ) scores.
By the end of the study we should notice decrease in DAS-28-CRP score and the Multidimensional Health Assessment Questionnaire (MDHAQ) scores.
Measured: 12 week
Secondary outcomes (1)
change in the serum level of the assessed biological markers
By the end of the study we should notice decrease in serum level of the assessed biological markers
- C-reactive protein (CRP).
- 8-hydroxydeoxyguanosine (8-OHdG).
- Interlukin-6 (IL-6).
- Leukotriene B4 (LTB4
Measured: 12 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2023
- Study start1 Jun 2024 (estimated)
- Primary completionOct 2024 (estimated)
- Study completionNov 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Tanta UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomized, double blind placebo controlled parallel study
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tanta University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yomna Abdelrafea Ahmed, Tanta University
- Investigators
- Dr/Tarek Mohamed, Professor, Study director, Tanta University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06108518
- Sponsor's protocol ID
- Carvedilol in active RA
- Status last verified
- Apr 2024
- First submitted
- 25 Oct 2023
- Last updated
- 16 Apr 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Ahmed YM, Messiha BA and Abo-Saif AA. Granisetron and carvedilol can protect experimental rats against adjuvant-induced arthritis. Immunopharmacol Immunotoxicol., 2017; 39(2):97-104. Aletaha D, and Smolen JS. Diagnosis and Management of Rheumatoid Arthritis: A Review. JAMA. 2018; 320 (13):1360-1372. Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569-2581. Arab HH and El-Sawalhi MM. Carvedilol alleviates adjuvant-induced arthritis and subcutaneous air pouch edema: Modulation of oxidative stress and inflammatory mediators. Toxicol Appl Pharmacol., 2013;268(2):241-248. Dijkshoorn B, Raadsen R and Nurmohamed MT. Cardiovascular Disease Risk in Rheumatoid Arthritis Anno 2022. J Clin Med., 2022 ;11(10):2704. El Miedany Y, El Gaafary M, Youssef SS, et al. Validity of the Developed Arabic Multidimensional Health Assessment Questionnaire for use in standard clinical care of patients with rheumatic diseases. Int J Rheum Dis., 2008; 11:224-236. Giollo A, Bissell LA and Buch MH. Cardiovascular outcomes of patients with rheumatoid arthritis prescribed disease modifying anti-rheumatic drugs: A review. Expert Opin Drug Saf., 2018 ;17(7):697-708. Guo Q, Wang Y, Xu D, et al. Rheumatoid arthritis: Pathological mechanisms and modern pharmacologic therapies. Bone Res., 2018; 6:15.
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study Evaluating the Effect of Carvedilol in Patients With Active Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT06108518
- Acronym / sponsor ID
- Carvedilol in active RA
- Conditions
- Rheumatoid Arthritis
- Keywords
- Carvedilol, Hypertension
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Tanta UniversityUniversity, hospital or other
- Study start
- 1 Jun 2024 (estimated)
- Primary completion
- Oct 2024 (estimated)
- Study completion
- Nov 2024 (estimated)
- First posted
- 31 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims at investigating the possible efficacy and safety of carvedilol as an adjunctive therapy in patients with active rheumatoid arthritis and hypertension.
Detailed description
heumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily affects the lining of the synovial joints and is associated with progressive disability, premature death, and socioeconomic burdens. It is characterized with chronic production of pro-inflammatory cytokines, which lead to cartilage and bone degradation that results in tissue destruction by the patients' immune system (Guo et al., 2018).
The high systemic inflammatory burden associated with RA appears to be a key driver of increased CV risk. This inflammatory state is linked to endothelial dysfunction and accelerated atherosclerosis (Giollo et al., 2018). Consequently, RA increases the risk of cardiovascular (CV) mortality by up to 50% compared with the general population and CV disease is the leading cause of death in RA patients. This leads to suggestion that reducing inflammation lowers CV risk in RA (Dijkshoorn et al., 2022).
Therapies targeting inflammation remain the mainstay of RA treatment such as non- steroidal anti-inflammatory drugs (NSAIDs), non-biologic and biologic disease-modifying anti-rheumatic drugs (DMARDs), immune-osuppressants, and corticosteroids. However, current treatment strategies have many adverse effects and a significant proportion of RA patients did not effectively respond to them (Aletaha and Smolen., 2018). Consequently, it is crucial to find new therapeutic approaches for the management of inflammation as well as the prevention of cardiovascular complications in rheumatoid arthritis patients.
Carvedilol is a non-selective β-blocker with α-adrenergic receptor antagonism properties which has been safely used in treatment of several cardiovascular disorders (Prajapati et al., 2017). Previous animal studies highlights evidences for the promising anti- arthritic effects of carvedilol that could be mediated through attenuation of leukocyte migration, alleviation of oxidative stress and suppression of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interlukin-6 (IL-6) and eicosanoids including prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) (Arab and El-Sawalhi, 2013; Ahmed et al., 2017; Osman et al., 2017).
Taken together, carvedilol has powerful antioxidant/anti-inflammatory properties; we aimed to investigate its protective potential against arthritis that may add further benefits for its clinical usefulness especially in RA patients with concomitant cardiovascular disorders
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- randomized, double blind placebo controlled parallel study
| Arm | Type | Receives |
|---|---|---|
| Control group | Placebo comparator | Drug: CarvedilolGroup1 (Placebo group; n=35) which will receive the standard treatment for RA plus placebo tablet for 3 months. |
| Treatment group | Active comparator | Drug: CarvedilolGroup 2 (Carvedilol group; n=35) which will receive the standard treatment for RA plus carvedilol 12.5mg once a day for 2 days; this is increased to 25 mg once a day or 12.5 mg twice a day for 3 months. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Patients with active rheumatoid arthritis (not in remission) according to American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 criteria i.e 28 joints disease activity score (DAS-28) >2.6.
- Patients with hypertension who are candidate to carvidolol.
- Age range between 18 and 60 years old.
- The studywillbecarriedoutbetween June 2023 and June 2025.
- Both sexes.
Key exclusion criteria (13 listed)
- Patients with congestive heart failure, other heart disease (arrhythmia, ischemic heart disease including angina and myocardial infarction).
- Patients with other inflammatory diseases and active infection.
- Patients with glaucoma.
- Patients with asthma, COPD, other lung diseases.
- Patients with hepatic and biliary diseases.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CarvedilolTreatment group will take carvedilol 12.5mg once a day for 2 days; this is increased to 25 mg once a day or 12.5 mg twice a day for 3 months. | Drug | Control group, Treatment group |
Primary outcome
change in DAS-28-CRP score and the Multidimensional Health Assessment Questionnaire (MDHAQ) scores.
Time frame: 12 week
By the end of the study we should notice decrease in DAS-28-CRP score and the Multidimensional Health Assessment Questionnaire (MDHAQ) scores.
1 secondary outcome
change in the serum level of the assessed biological markers
Time frame: 12 week
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2024.
- BackgroundAhmed YM, Messiha BA and Abo-Saif AA. Granisetron and carvedilol can protect experimental rats against adjuvant-induced arthritis. Immunopharmacol Immunotoxicol., 2017; 39(2):97-104. Aletaha D, and Smolen JS. Diagnosis and Management of Rheumatoid Arthritis: A Review. JAMA. 2018; 320 (13):1360-1372. Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569-2581. Arab HH and El-Sawalhi MM. Carvedilol alleviates adjuvant-induced arthritis and subcutaneous air pouch edema: Modulation of oxidative stress and inflammatory mediators. Toxicol Appl Pharmacol., 2013;268(2):241-248. Dijkshoorn B, Raadsen R and Nurmohamed MT. Cardiovascular Disease Risk in Rheumatoid Arthritis Anno 2022. J Clin Med., 2022 ;11(10):2704. El Miedany Y, El Gaafary M, Youssef SS, et al. Validity of the Developed Arabic Multidimensional Health Assessment Questionnaire for use in standard clinical care of patients with rheumatic diseases. Int J Rheum Dis., 2008; 11:224-236. Giollo A, Bissell LA and Buch MH. Cardiovascular outcomes of patients with rheumatoid arthritis prescribed disease modifying anti-rheumatic drugs: A review. Expert Opin Drug Saf., 2018 ;17(7):697-708. Guo Q, Wang Y, Xu D, et al. Rheumatoid arthritis: Pathological mechanisms and modern pharmacologic therapies. Bone Res., 2018; 6:15.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dr/Eman Ibrahim, Lecturer contact
Dr/Tarek Mohamed, Professor study director
Tanta University
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Carvedilol in people with Rheumatoid Arthritis, run by Tanta University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 16 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yomna Abdelrafea, Bachelor (01021683076, umna.a.rafea@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
change in DAS-28-CRP score and the Multidimensional Health Assessment Questionnaire (MDHAQ) scores. (time frame: 12 week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06108518, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2024.