Antibiotic Treatment of Gulf War Veterans' Illnesses

Sponsor

US Department of Veterans Affairs (U.S. Fed)

Overall Status

Completed

CT.gov ID

NCT00007735

Collaborator

Pfizer (Industry), United States Department of Defense (U.S. Fed)

450

Enrollment

Locations

Duration (Months)

16.7

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Persian Gulf Syndrome Mycoplasma Infections	Drug: Doxycycline (200mg/day) or Placebo	Phase 3

Detailed 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.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double

Official Title:

CSP #475 - Persian Gulf - Antibiotic Treatment Trial of Gulf War Veterans' Illnesses

Study Start Date :

Jan 1, 1999

Study Completion Date :

Oct 1, 2001

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

All veterans deployed to the Gulf War between August, 1990 and August, 1991 having at least two of the following symptoms: Fatigue, musculoskeletal pain or neurocognitive dysfunction. Mycoplasma positive

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vamc - Birmingham, Al	Birmingham	Alabama	United States	35233
2	Naval Health Research Center Merchant Illness Divi	San Diego	California	United States	92152
3	Uniformed Services University Department of Psychi	Washington	District of Columbia	United States	20307-5001
4	Vamc - Augusta, Ga	Augusta	Georgia	United States	30904-6285
5	Vamc - Hines,Il	Hines	Illinois	United States	60141
6	Vamc - New Orleans, La	New Orleans	Louisiana	United States	70146
7	Vamc - Boston, Ma	Boston	Massachusetts	United States	02130
8	Vamc - Omaha, NE	Omaha	Nebraska	United States	68105
9	Vamc - Manchester,Nh	Manchester	New Hampshire	United States	03103
10	Vamc - East Orange, Nj	East Orange	New Jersey	United States	07018
11	Vamc - Albuquerque, Nm	Albuquerque	New Mexico	United States	87108
12	Vamc - Albany, Ny	Albany	New York	United States	12208
13	Vamc - Bronx,Ny	Bronx	New York	United States	10468
14	Vamc - Brooklyn, Ny	Brooklyn	New York	United States	11209
15	Vamc - Durham, Nc	Durham	North Carolina	United States	27705
16	Vamc - Fargo, Nd	Fargo	North Dakota	United States	58102-2498
17	Vamc - Dayton, Oh	Kettering	Ohio	United States	45429
18	Vamc - Oklahoma City, Ok	Oklahoma City	Oklahoma	United States	73104
19	Vamc - Philadelphia, Pa	Philadelphia	Pennsylvania	United States	19104
20	Vamc - Providence, Ri	Providence	Rhode Island	United States	02908-4799
21	Vamc - Charleston, Sc	Charleston	South Carolina	United States	29401-5799
22	Vamc - Nashville, Tn	Nashville	Tennessee	United States	37212-2637
23	Vamc - Houston, Tx	Houston	Texas	United States	77030-4298
24	Vamc - White River Junction	White River Junction	Vermont	United States	05009
25	Vamc - Richmond, Va	Richmond	Virginia	United States	23249
26	Vamc - Milwaukee, Wi	Milwaukee	Wisconsin	United States	53295
27	Vamc - San Juan, Pr	San Juan		Puerto Rico	00927