Study of Adalimumab to Lower Cardiovascular Risk in RA Patients With Well Controlled Joint Disease

NCT01893996 | Completed Phase 4 DMC

• 1 other identifier: 12-09816
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief Summary

Rheumatoid arthritis patients are at increased risk of cardiovascular disease because of systemic inflammation that can persist even in patients with well-controlled joint disease. We hypothesize that adding an anti-tumor necrosis factor medication, adalimumab, to standard non-biologic therapy for rheumatoid arthritis will improve endothelial function (reduce cardiovascular risk) in these patients. The design of the trial is as follows: 18 month prospective, randomized, double-blind crossover trial comparing the addition of adalimumab to the addition of placebo. The primary endpoint is a change in endothelial cell function, as detected by brachial artery FMD, at 6 months of adalimumab treatment compared to 6 months of placebo.

Conditions

Rheumatoid Arthritis; Cardiovascular Disease

Keywords

rheumatoid; arthritis; cardiovascular; adalimumab; tnf; biologic

Outcome Measures

Primary Outcomes (1)

• Change in Endothelial Function

  The primary endpoint is the change in endothelial cell function, as detected by brachial artery flow-mediated dilitation.

  Weeks 0, 13, 26, 52, 65, 78

Secondary Outcomes (1)

• Change in vascular inflammation

  Weeks 0 and 26

Other Outcomes (1)

• Improvement in HDL function

  Weeks 0,26,52,78

Study Arms (2)

Adalimumab

EXPERIMENTAL

Active Study Drug is Adalimumab (Humira) which is FDA approved to treat rheumatoid arthritis since 2003.

Drug: Adalimumab

Placebo

PLACEBO COMPARATOR

Placebo is inert and matches study drug, including the pre-filled syringe, and is supplied by Abbvie, the study drug manufacturer.

Drug: Placebo

Interventions

Adalimumab DRUG

Patients will be randomized 1:1 to receive either adalimumab or placebo for the first 26 weeks of the trial, and then after a 26 week washout period, will be crossed over into the other arm (either placebo or adalimumab) for weeks 52-78.

Also known as: Humira

Adalimumab

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject must be able and willing to give written informed consent and comply with the requirements of the study protocol.
• Diagnosis of Rheumatoid Arthritis by ACR 1987 or ACR/EULAR 2010 criteria.
• Low RA disease activity as defined by DAS28 \< 3.2
• No anti-TNF medication or other biologic agent (abatacept, rituximab, or tocilizumab) within the 12 months prior to enrollment.
• If taking methotrexate, then on a stable dose between 7.5 mg and 25 mg (PO or SQ) weekly for at least 3 months prior to randomization. If on a DMARD other than methotrexate, then that DMARD must be at a stable therapeutic dose for at least 3 months prior to randomization.
• If taking prednisone, then a stable dose of less than or equal to 10 mg/daily for at least 1 month prior to randomization
• If NSAID taken on a regular, daily schedule, then patient must be on a stable dose for one week prior to FMD studies. PRN use is excluded within 1 week of FMD studies.
• Age \> 18
• Subject must be able and willing to self-administer SQ injections or have available qualified person(s) or caregiver to administer SQ injections
• Negative serum pregnancy test (for women of child bearing age)
• Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment
• Adequate renal function as indicated by serum creatinine \< 2.0.
• No use of phosphodiesterase type 5 inhibitors (PDE5) (i.e. sildenafil, tadalafil, and vardenafil) 1 week prior to the study and during the course of the study.

You may not qualify if:

• Use of an anti-TNF or other biologic medication (Including but not limited to abatacept, rituximab, or tocilizumab) within the previous 12 months.
• Prior history of MI, CVA, CABG, PTCA, or peripheral vascular disease
• SBP \> 140/90 at two months prior to study enrollment
• Diabetes mellitus requiring insulin therapy
• The following laboratory parameters at the Screening visit
• Neutropenia (absolute neutrophil count \< 1,500/microliter \[ L\]);
• Thrombocytopenia (platelets \< 100,000/ L);
• Anemia (hemoglobin \< 8 g/dL);
• Greater than or equal to 3 times the upper limit of normal (ULN) for either of the following liver function tests (LFTs): aspartate transaminase (AST) or alanine transaminase (ALT);
• Renal insufficiency (serum creatinine\> 2.0 mg/dL)
• Purified protein derivative (PPD) test of \> 5 mm induration regardless of prior BacilleCalmette Guerin vaccine administration or positive QuantiFERON®-TB Gold In-Tube Test (QFT-G\_IT) without documentation of completed treatment or evidence of ongoing treatment of latent tuberculosis (TB) for 30 days. Subjects with active TB infection are excluded.
• History of positive PPD, positive QuantiFERON®-TB Gold In-Tube Test (QFT-G\_IT), or chest x-ray findings indicative of prior TB infection, without documentation of either treatment for TB infection or chemoprophylaxis for TB exposure
• Prednisone dose \> 10 mg/day (or equivalent dose of another corticosteroid) within 1 month of randomization
• Presence of open leg ulcers
• Chronic or persistent infection including but not limited to human immunodeficiency virus \[HIV\],hepatitis B, hepatitis C, listeriosis, TB, or other opportunistic infection)

Sponsors & Collaborators

• Jonathan Graf: lead
• American College of Rheumatology Research and Education Foundation: collaborator
• AbbVie: collaborator

Study Sites (1)

University of California San Francisco/San Francisco General Hospital

San Francisco, California, 94110, United States

Location

Related Links

• UCSF Division of Rheumatology: Clinical \& Epidemiological Research

MeSH Terms

Conditions

Arthritis, Rheumatoid; Cardiovascular Diseases; Arthritis

Interventions

Adalimumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jonathan Graf, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Peter Ganz, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: July 2, 2013
• First Posted: July 9, 2013
• Study Start: July 1, 2013
• Primary Completion: July 1, 2017
• Study Completion: July 1, 2017
• Last Updated: April 9, 2021

Record last verified: 2021-04

Locations

US (1)