Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00007735 |
| Other study ID # |
475 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
January 1999 |
| Est. completion date |
October 2001 |
Study information
| Verified date |
February 2007 |
| Source |
VA Office of Research and Development |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
In 1990 and 1991, the U.S. deployed approximately 700,000 troops to the Persian Gulf to
liberate Kuwait from Iraqi occupation. While there were few casualties associated with the
Gulf War, many individuals returned from this conflict with unexplained symptoms and
illnesses. This constellation of symptoms has been termed Gulf War Veterans' Illnesses (GWI).
Although several explanations have been offered as to the cause of GWI, none of the putative
etiologic agents or conditions is currently supported by sufficient evidence. One explanation
that has received fairly widespread attention is systemic Mycoplasma fermentans infection. It
is the purpose of this study to determine if antibiotic treatment directed against Mycoplasma
species (i.e. doxycycline) will improve functioning and symptoms in deployed Gulf War
veterans with GWI.
Description:
Primary Hypothesis: The primary hypothesis of this study is that antibiotic treatment
directed against Mycoplasmaspecies will improve functional status of patients with Gulf War
Veterans' Illnesses (GWI) who are tested as mycoplasma positive at baseline. Specifically,
the primary objective of the study is to determine whether a 12 month course of doxycycline
treatment in deployed Gulf War veterans presenting with symptoms of GWI and testing as
mycoplasma positive improves functional status compared to placebo.
Secondary Hypotheses: Secondary objectives of this study are (1) to determine whether
doxycycline treatment reduces symptoms of GWI including pain, fatigue and neurocognitive
concerns, (2) to determine whether doxycycline treatment converts mycoplasma positive
patients to mycoplasma negative status, and (3) to determine if the benefits of 12 months
doxycycline treatment persist after termination of treatment.
Intervention: Patients are randomized to either doxycycline (200mg/day) or placebo which they
are instructed to take in the morning.
Primary Outcomes: The primary outcome measure is improvement in the Physical Component Scale
(PCS) of the SF-36V at follow-up relative to baseline. The primary end point will be the
proportion of patients with more than a seven unit increase in the PCS at 12 months.
Important secondary outcome measures are a pain scale (McGill Pain Questionnaire), a fatigue
scale (Multidimensional Fatigue Inventory), a neurocognitive symptoms scale (Cognitive
Failures Questionnaire), and a GWI Symptom Checklist developed specifically for this study.
Study Abstract: In 1990 and 1991, the U.S. deployed approximately 700,000 troops to the
Persian Gulf to liberate Kuwait from Iraqi occupation. While there were few casualties
associated with the Gulf War, many individuals returned from this conflict with unexplained
symptoms and illnesses. This constellation of symptoms has been termed Gulf War Veterans'
Illnesses (GWI). Although several explanations have been offered as to the cause of GWI, none
of the putative etiologic agents or conditions is currently supported by sufficient evidence.
One explanation that has received fairly widespread attention is systemic Mycoplasma
fermentans infection. It is the purpose of this study to determine if antibiotic treatment
directed against Mycoplasma species (i.e. doxycycline) will improve functioning and symptoms
in deployed Gulf War veterans with GWI.
The study is a 30 month, prospective, randomized, double-blind clinical trial. All veterans
deployed to the Gulf War between August, 1990 and August, 1991 will be eligible. Patients
will be considered to have GWI if they have at least two of three symptoms (fatigue,
musculoskeletal pain, neurocognitive dysfunction) that began after August, 1990 and that have
lasted more than six months up to the present. Four hundred and fifty of these GWI patients
from 28 medical centers who test positive for Mycoplasma fermentans, Mycoplasma gentalium
and/or Mycoplasma pneumoniae at baseline and have no exclusion criteria will be entered into
the study over a one year recruitment period. These mycoplasma positive species patients will
be randomized to one of two treatment groups: (1) patients treated with doxycycline for 12
months and (2) patients given placebo for 12 months. Each patient will receive study
medication for 12 months and will be followed for an additional six months after the
termination of medications. Patients will be seen monthly during the medication phase and at
18 months. Major evaluations will be completed at baseline and at 3, 6, 9, 12 and 18 months.
Patients assigned to doxycycline will receive 200mg/day, which they will be instructed to
take in the morning.
MAIN MANUSCRIPT - Submitted to New England Journal of Medicine on February 22, 2002. On May
10, 2002, New Englad Journal of Medicine rejected the manuscript. Manuscript was submitted to
LANCET on June 17, 2002 and rejected on July 29, 2002. Manuscript was submitted to JAMA on
August 30, 2002 and rejected on September 6, 2002. Manuscript has been resubmitted to JAMA on
March 24, 2003.
