Catherine D. Bacheller, Joseph Lentino, Marvin J. Bittner, Edward S. Wong, Richard J. Hamill, Lisa L. Dever, Manisha Thakore, Kenneth H. Wilson, Jack M. Bernstein, Luis Montalvo, Rebecca A. Horney, Annette L. Wiseman, Margaret A. K. Ryan, Kathy D. Boardman, James K. Schmitt, Christopher Nice, Victor Gordan, Dorothy Norwood, Cliff Robinson, Fredric Silverblatt, Pierre DeJace, David R. Wagner, Joel B. Baseman, Lisa Beck, Arnold B. Gorin, L. W. Preston Church, Bruce S. Ribner, Prabhakar Guduru, Christine Handanos, Lewis E. Kazis, Michael P. Everson, Larry I. Lutwick, Douglas S. Kernodle, Sam T. Donta, Suzanne E. Martin, Thomas Taylor, John R. Feussner, H. Ralph Schumacher, Warren D. Blackburn, Charles C. Engel, Aldona L. Baltch, Raymond P. Smith, Ronald Greenfield, Javier Figueroa, Brian Catto, Sheldon T. Brown, Joseph F. Collins, and Robert Cooper
Background It has been hypothesized that certain Mycoplasma species may cause Gulf War veterans' illnesses (GWVIs), chronic diseases characterized by pain, fatigue, and cognitive symptoms, and that affected patients may benefit from doxycycline treatment. Objective To determine whether a 12-month course of doxycycline improves functional status in Gulf War veterans with GWVIs. Design A randomized, double-blind, placebo-controlled clinical trial with 12 months of treatment and 6 additional months of follow-up. Setting 26 U.S. Department of Veterans Affairs and 2 U.S. Department of Defense medical centers. Participants 491 deployed Gulf War veterans with GWVIs and detectable Mycoplasma DNA in the blood. Intervention Doxycycline, 200 mg, or matching placebo daily for 12 months. Measurements The primary outcome was the proportion of participants who improved more than 7 units on the Physical Component Summary score of the Veterans Short Form-36 General Health Survey 12 months after randomization. Secondary outcomes were measures of pain, fatigue, and cognitive function and change in positivity for Mycoplasma species at 6, 12, and 18 months after randomization. Results No statistically significant differences were found between the doxycycline and placebo groups for the primary outcome measure (43 of 238 participants [18.1%] vs. 42 of 243 participants [17.3%]; difference, 0.8 percentage point [95% CI, -6.5 to 8.0 percentage points]; P > 0.2) or for secondary outcome measures at 1 year. In addition, possible differences in outcomes at 3 and 6 months were not apparent at 9 or 18 months. Participants in the doxycycline group had a higher incidence of nausea and photosensitivity. Limitations Adherence to treatment after 6 months was poor. Conclusion Long-term treatment with doxycycline did not improve outcomes of GWVIs at 1 year.