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.