Previous randomized, controlled clinical trials suggest that oral tetracyclines may reduce the symptoms of joint inflammation in rheumatoid arthritis (RA). This class of antibiotics has well-described antimicrobial effects as well as anti-collagenase activity. Collagenase is an enzyme that degrades cartilage and bone and is believed to be important in the pathogenesis of RA. This study evaluated the safety and potential clinical efficacy of I.V. doxycycline therapy in 31 patients with RA and explored whether any improvements in arthritis from the doxycycline were due to its antibacterial actions or ability to reduce the activity of collagenase. The three objectives of this study were: 1) To determine the feasibility, safety, and potential clinical efficacy of I.V. doxycycline therapy in RA and explore whether this agent ameliorates clinical manifestations of this disease by suppressing bacterial infection or matrix metalloproteinases (MMP) activity; 2) To determine whether daily and weekly treatment with I.V. doxycycline can reduce urinary excretion of collagen crosslinks in patients with RA and potentially retard joint damage; and 3) To explore the potential effects of daily and weekly I.V. doxcycline therapy on biochemical markers of cartilage proteoglycan degradation; and 4) to determine whether IV doxycycline can reduce expression of nitric oxide synthase type 2 expressed by circulatory monocytes. Patients were randomized into 3 groups: Group I received I.V. doxycycline and oral placebo, Group II will received I.V. placebo and oral azithromycin, and Group III received I.V. and oral placebo. The I.V. therapy was delivered through a peripheral long-line catheter. The initial treatment phase consisted of daily infusions and oral therapy for 21 days. The second treatment phase consisted of weekly infusions administered from week 4 through 11. Results: The study is closed and a Final Report was submitted to the NIH on December 29, 1998. Thirty-one patients were enrolled between April of 1995 and February 1998. The study population included various ethnic backgrounds, such as African- American, Caucasian, and Native American and was predominantly female (24/7). Only 4 patients withdrew from the trial before the day 112 visit. Three patients discontinued the study drug after day 28 because of worsening arthritis and one patient withdrew at day 56 when she was diagnosed with breast cancer. Thirteen (42%) of the patients experienced at least one infusion-related event during the trial. These events included catheter site tenderness/pain/redness, symptoms of burning during the infusion, site-related skin rash from adhesive tape, catheter infiltration, signs of localized infection at the catheter site, clotting of the catheter or line, and thrombophlebitis. None of these events were classified as serious. Most of the patients experienced at least 1 adverse event, which were most commonly gastrointestinal or neurologic in origin. The most frequent adverse events apart from the infusion-related complications included headache (8 patients), abdominal pain (6 patients), fatigue (6 patients), nausea/vomiting (5 patients, vaginitis (5 patients), loose stools/diarrhea 93 patients), dizziness/lightheadedness (3 patients), and decreased appetite (3 patients). The results of the present study do not provide evidence that i.v. doxycycline therapy reduces the signs or symptoms of RA. These data must be interpreted with caution because the study was not designed to provide adequate statistical power to answer this question. The present study does show that this treatment approach is feasible and does not cause unacceptable toxicities. However, no significant differences were noted among treatment groups in the primary endpoints. The tender joint count dropped only slightly in all of the 3 treatment groups. This result is compatible with little or no immediate clinical effect from the 3 weeks of i.v. doxycycline therapy. Significance: There are no future plans since doxycycline did not improve the primary endpoints.

Project Start
1998-12-01
Project End
1999-11-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
38
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Duke University
Department
Type
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
Askie, Lisa M; Darlow, Brian A; Finer, Neil et al. (2018) Association Between Oxygen Saturation Targeting and Death or Disability in Extremely Preterm Infants in the Neonatal Oxygenation Prospective Meta-analysis Collaboration. JAMA 319:2190-2201
Srinivasan, Lakshmi; Page, Grier; Kirpalani, Haresh et al. (2017) Genome-wide association study of sepsis in extremely premature infants. Arch Dis Child Fetal Neonatal Ed 102:F439-F445
Denson, Lee A; McDonald, Scott A; Das, Abhik et al. (2017) Early Elevation in Interleukin-6 is Associated with Reduced Growth in Extremely Low Birth Weight Infants. Am J Perinatol 34:240-247
James, Jennifer; Munson, David; DeMauro, Sara B et al. (2017) Outcomes of Preterm Infants following Discussions about Withdrawal or Withholding of Life Support. J Pediatr 190:118-123.e4
Younge, Noelle; Goldstein, Ricki F; Bann, Carla M et al. (2017) Survival and Neurodevelopmental Outcomes among Periviable Infants. N Engl J Med 376:617-628
Archer, Stephanie Wilson; Carlo, Waldemar A; Truog, William E et al. (2016) Improving publication rates in a collaborative clinical trials research network. Semin Perinatol 40:410-417
Ahmed, Zuhayer; Prasad, Indrajit; Rahman, Hafizur et al. (2016) A Male with Extreme Subcutaneous Insulin Resistance: A Case Report. Rom J Diabetes Nutr Metab Dis 23:209-213
Phelps, Dale L; Ward, Robert M; Williams, Rick L et al. (2016) Safety and pharmacokinetics of multiple dose myo-inositol in preterm infants. Pediatr Res 80:209-17
Barroso, Julie; Leserman, Jane; Harmon, James L et al. (2015) Fatigue in HIV-Infected People: A Three-Year Observational Study. J Pain Symptom Manage 50:69-79
Stafford-Smith, Mark; Li, Yi-Ju; Mathew, Joseph P et al. (2015) Genome-wide association study of acute kidney injury after coronary bypass graft surgery identifies susceptibility loci. Kidney Int 88:823-32

Showing the most recent 10 out of 128 publications