Benefits and harms of doxycycline treatment for Gulf War Veterans' illnesses: A randomized, double-blind, placebo-controlled trial

Sam T. Donta, Charles C. Engel, Joseph F. Collins, Joel B. Baseman, Lisa L. Dever, Thomas Taylor, Kathy D. Boardman, Lewis E. Kazis, Suzanne E. Martin, Rebecca A. Horney, Annette L. Wiseman, Douglas S. Kernodle, Raymond P. Smith, Aldona L. Baltch, Christine Handanos, Brian Catto, Luis Montalvo, Michael Everson, Warren Blackburn, Manisha ThakoreSheldon T. Brown, Larry Lutwick, Dorothy Norwood, Jack Bernstein, Catherine Bacheller, Bruce Ribner, L. W Preston Church, Kenneth H. Wilson, Prabhakar Guduru, Robert Cooper, Joseph Lentino, Richard J. Hamill, Arnold B. Gorin, Victor Gordan, David Wagner, Cliff Robinson, Pierre DeJace, Ronald Greenfield, Lisa Beck, Marvin Bittner, H. Ralph Schumacher, Fredric Silverblatt, James Schmitt, Edward Wong, Margaret A K Ryan, Javier Figueroa, Christopher Nice, John R. Feussner

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)85-94+I
JournalAnnals of Internal Medicine
Volume141
Issue number2
StatePublished - Jul 20 2004
Externally publishedYes

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Gulf War
Doxycycline
Veterans
Placebos
Mycoplasma
Outcome Assessment (Health Care)
Random Allocation
Therapeutics
Fatigue
Pain
Neurobehavioral Manifestations
United States Department of Veterans Affairs
Controlled Clinical Trials
Health Surveys
Cognition
Nausea
Chronic Disease
DNA
Incidence

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Donta, S. T., Engel, C. C., Collins, J. F., Baseman, J. B., Dever, L. L., Taylor, T., ... Feussner, J. R. (2004). Benefits and harms of doxycycline treatment for Gulf War Veterans' illnesses: A randomized, double-blind, placebo-controlled trial. Annals of Internal Medicine, 141(2), 85-94+I.

Benefits and harms of doxycycline treatment for Gulf War Veterans' illnesses : A randomized, double-blind, placebo-controlled trial. / Donta, Sam T.; Engel, Charles C.; Collins, Joseph F.; Baseman, Joel B.; Dever, Lisa L.; Taylor, Thomas; Boardman, Kathy D.; Kazis, Lewis E.; Martin, Suzanne E.; Horney, Rebecca A.; Wiseman, Annette L.; Kernodle, Douglas S.; Smith, Raymond P.; Baltch, Aldona L.; Handanos, Christine; Catto, Brian; Montalvo, Luis; Everson, Michael; Blackburn, Warren; Thakore, Manisha; Brown, Sheldon T.; Lutwick, Larry; Norwood, Dorothy; Bernstein, Jack; Bacheller, Catherine; Ribner, Bruce; Church, L. W Preston; Wilson, Kenneth H.; Guduru, Prabhakar; Cooper, Robert; Lentino, Joseph; Hamill, Richard J.; Gorin, Arnold B.; Gordan, Victor; Wagner, David; Robinson, Cliff; DeJace, Pierre; Greenfield, Ronald; Beck, Lisa; Bittner, Marvin; Schumacher, H. Ralph; Silverblatt, Fredric; Schmitt, James; Wong, Edward; Ryan, Margaret A K; Figueroa, Javier; Nice, Christopher; Feussner, John R.

In: Annals of Internal Medicine, Vol. 141, No. 2, 20.07.2004, p. 85-94+I.

Research output: Contribution to journalArticle

Donta, ST, Engel, CC, Collins, JF, Baseman, JB, Dever, LL, Taylor, T, Boardman, KD, Kazis, LE, Martin, SE, Horney, RA, Wiseman, AL, Kernodle, DS, Smith, RP, Baltch, AL, Handanos, C, Catto, B, Montalvo, L, Everson, M, Blackburn, W, Thakore, M, Brown, ST, Lutwick, L, Norwood, D, Bernstein, J, Bacheller, C, Ribner, B, Church, LWP, Wilson, KH, Guduru, P, Cooper, R, Lentino, J, Hamill, RJ, Gorin, AB, Gordan, V, Wagner, D, Robinson, C, DeJace, P, Greenfield, R, Beck, L, Bittner, M, Schumacher, HR, Silverblatt, F, Schmitt, J, Wong, E, Ryan, MAK, Figueroa, J, Nice, C & Feussner, JR 2004, 'Benefits and harms of doxycycline treatment for Gulf War Veterans' illnesses: A randomized, double-blind, placebo-controlled trial', Annals of Internal Medicine, vol. 141, no. 2, pp. 85-94+I.
Donta, Sam T. ; Engel, Charles C. ; Collins, Joseph F. ; Baseman, Joel B. ; Dever, Lisa L. ; Taylor, Thomas ; Boardman, Kathy D. ; Kazis, Lewis E. ; Martin, Suzanne E. ; Horney, Rebecca A. ; Wiseman, Annette L. ; Kernodle, Douglas S. ; Smith, Raymond P. ; Baltch, Aldona L. ; Handanos, Christine ; Catto, Brian ; Montalvo, Luis ; Everson, Michael ; Blackburn, Warren ; Thakore, Manisha ; Brown, Sheldon T. ; Lutwick, Larry ; Norwood, Dorothy ; Bernstein, Jack ; Bacheller, Catherine ; Ribner, Bruce ; Church, L. W Preston ; Wilson, Kenneth H. ; Guduru, Prabhakar ; Cooper, Robert ; Lentino, Joseph ; Hamill, Richard J. ; Gorin, Arnold B. ; Gordan, Victor ; Wagner, David ; Robinson, Cliff ; DeJace, Pierre ; Greenfield, Ronald ; Beck, Lisa ; Bittner, Marvin ; Schumacher, H. Ralph ; Silverblatt, Fredric ; Schmitt, James ; Wong, Edward ; Ryan, Margaret A K ; Figueroa, Javier ; Nice, Christopher ; Feussner, John R. / Benefits and harms of doxycycline treatment for Gulf War Veterans' illnesses : A randomized, double-blind, placebo-controlled trial. In: Annals of Internal Medicine. 2004 ; Vol. 141, No. 2. pp. 85-94+I.
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title = "Benefits and harms of doxycycline treatment for Gulf War Veterans' illnesses: A randomized, double-blind, placebo-controlled trial",
abstract = "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.",
author = "Donta, {Sam T.} and Engel, {Charles C.} and Collins, {Joseph F.} and Baseman, {Joel B.} and Dever, {Lisa L.} and Thomas Taylor and Boardman, {Kathy D.} and Kazis, {Lewis E.} and Martin, {Suzanne E.} and Horney, {Rebecca A.} and Wiseman, {Annette L.} and Kernodle, {Douglas S.} and Smith, {Raymond P.} and Baltch, {Aldona L.} and Christine Handanos and Brian Catto and Luis Montalvo and Michael Everson and Warren Blackburn and Manisha Thakore and Brown, {Sheldon T.} and Larry Lutwick and Dorothy Norwood and Jack Bernstein and Catherine Bacheller and Bruce Ribner and Church, {L. W Preston} and Wilson, {Kenneth H.} and Prabhakar Guduru and Robert Cooper and Joseph Lentino and Hamill, {Richard J.} and Gorin, {Arnold B.} and Victor Gordan and David Wagner and Cliff Robinson and Pierre DeJace and Ronald Greenfield and Lisa Beck and Marvin Bittner and Schumacher, {H. Ralph} and Fredric Silverblatt and James Schmitt and Edward Wong and Ryan, {Margaret A K} and Javier Figueroa and Christopher Nice and Feussner, {John R.}",
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T1 - Benefits and harms of doxycycline treatment for Gulf War Veterans' illnesses

T2 - A randomized, double-blind, placebo-controlled trial

AU - Donta, Sam T.

AU - Engel, Charles C.

AU - Collins, Joseph F.

AU - Baseman, Joel B.

AU - Dever, Lisa L.

AU - Taylor, Thomas

AU - Boardman, Kathy D.

AU - Kazis, Lewis E.

AU - Martin, Suzanne E.

AU - Horney, Rebecca A.

AU - Wiseman, Annette L.

AU - Kernodle, Douglas S.

AU - Smith, Raymond P.

AU - Baltch, Aldona L.

AU - Handanos, Christine

AU - Catto, Brian

AU - Montalvo, Luis

AU - Everson, Michael

AU - Blackburn, Warren

AU - Thakore, Manisha

AU - Brown, Sheldon T.

AU - Lutwick, Larry

AU - Norwood, Dorothy

AU - Bernstein, Jack

AU - Bacheller, Catherine

AU - Ribner, Bruce

AU - Church, L. W Preston

AU - Wilson, Kenneth H.

AU - Guduru, Prabhakar

AU - Cooper, Robert

AU - Lentino, Joseph

AU - Hamill, Richard J.

AU - Gorin, Arnold B.

AU - Gordan, Victor

AU - Wagner, David

AU - Robinson, Cliff

AU - DeJace, Pierre

AU - Greenfield, Ronald

AU - Beck, Lisa

AU - Bittner, Marvin

AU - Schumacher, H. Ralph

AU - Silverblatt, Fredric

AU - Schmitt, James

AU - Wong, Edward

AU - Ryan, Margaret A K

AU - Figueroa, Javier

AU - Nice, Christopher

AU - Feussner, John R.

PY - 2004/7/20

Y1 - 2004/7/20

N2 - 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.

AB - 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.

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