Gulf War IllnessPhase 2REGIONSNCT01846182
Research Examining Gulf War Illness in Our Nations Service Members
A Phase 2 study testing Duloxetine and Pregabalin in people with Gulf War Illness, run by VA Office of Research and Development at 2 sites in United States.
Trial summary
At least 1 in 4 of the 700,000 U.S. Veterans who served in the 1990-1991 Gulf War suffer from Gulf War Illness (GWI). Despite considerable research, effective treatments remain elusive. Read more about this study
- Who is it for?
- Ages 44 to 70 years
- Conditions the study is for
- Gulf War Illness
- What is being tested?
- Duloxetine and Pregabalin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 112 participants
- Where
- 2 sitesUnited States
- Study dates
- 24 Jun 2015to 1 Aug 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 44 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Living in Central Texas near Killeen, Austin, Temple or Waco
- Served on active military duty and deployed to the Persian Gulf region for some period between August 1990 \& July 1991
- English speaking and able to understand the consent form and study questionnaires
- Willing to be randomized to treatment and participate in 1-month follow up
- men \& women between the ages of 43 to 70
- meet Kansas GWI case definition for the diagnosis of GWI
- report a baseline score > 4 on a 10-point Pain Visual Analog Scale (VAS)
- female participants of childbearing potential must test negative for pregnancy at the time of enrollment based on a urine pregnancy test and agree to use a reliable method of birth control (for example, oral contraceptives or Norplant; a reliable barrier method of birth control [diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam); intrauterine devices; partner with vasectomy; or abstinence) during the study and for 2 months following the last dose of the study drug. [Note that this inclusion criterion applies only to females of childbearing potential. Females of childbearing potential are defined as women not surgically sterilized and between menarche and 2 years post-menopause.]
Who cannot join
- Unstable or poorly controlled chronic medical illness such as Diabetes type-II, Hypertension (HTN), heart disease, endocrine disorders, narrow angle glaucoma
- Significant Central Nervous System disease including transient ischemic attacks (TIAs) or stroke, Dementia, syncopal episodes, severe head trauma, multiple sclerosis
- Serious or advanced heart disease or clinically relevant abnormal electrocardiogram (ECG), postural hypotension
- Untreated sleep apnea or body mass index placing patients at risk for undiagnosed sleep apnea (BMI> 35 kg/m2)
- Diabetes type-I and patients with Diabetes type-II associated with peripheral neuropathy, hepatitis, liver failure/cirrhosis
- End stage renal disease
Show all 16Show fewer
- History of hypersensitivity reaction to pregabalin, duloxetine, venlafaxine; active treatment with duloxetine or pregabalin; History of failure of duloxetine or pregabalin at therapeutic doses; history of angioedema reaction to pregabalin
- Active systemic infectious disease such as tuberculosis and HIV, shingles
- Autoimmune mediated illnesses such as systemic lupus erythematosis, rheumatoid arthritis, scleroderma
- History of mental illness requiring hospitalization (depression, bipolar illness, post traumatic stress disorder, history of suicide attempts, psychosis, schizophrenia spectrum); Current major depression of dysthymia; patients lacking capacity to make medical decisions
- Use of monoamine oxidase inhibitors (MAOIs) within 2 weeks of evaluation; Active ongoing use of the following agents: desvenlafaxine, fenfluramine, linezolid, milnacipran, phentermine, tryptophan, tramadol, opiates
- Current (meets criterion within the last 6 months) for drug or alcohol dependence (except for nicotine and caffeine)
- Cancer other than non-melanoma skin cancers
- Women who are pregnant or desire to become pregnant, breastfeeding, who use unreliable contraception methods
- Those with occupations requiring use and/or operation of hazardous heavy equipment or professional drivers
- Patients for whom the potential risk outweighs the potential benefit in the opinion of the treating psychiatrist
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Central Texas Veterans Health Care System, Temple, TX
Temple, Texas, 76504
Central Texas Veterans Health Care System Waco VA Medical Center, Waco, TX
Waco, Texas, 76711
About this study
Official title: RCT of Duloxetine & Pregabalin for the Treatment of Gulf War Illness in Veterans
At least 1 in 4 of the 700,000 U.S. Veterans who served in the 1990-1991 Gulf War suffer from Gulf War Illness (GWI). Despite considerable research, effective treatments remain elusive. GWI refers to a complex of symptoms that typically include widespread chronic pain, persistent headache, memory and concentration problems, gastrointestinal difficulties, sleep disturbances and unexplained fatigue. These symptoms are similar to that of fibromyalgia syndrome (FMS), another multi-symptom condition. Whereas, effective treatments for GWI have yet to be found, the FDA has approved duloxetine and pregabalin for the treatment of FMS. The lack of progress in finding effective treatments for GWI, and the similarities between GWI and FMS, provides a rationale for determining if these medications can provide relief to Veterans who suffer from GWI. This randomized controlled trial will test the efficacy of Duloxetine and Pregabalin for treating Gulf War Veterans who suffer from GWI.
Read the detailed description
At least 1 in 4 of the 700,000 U.S. Veterans who served in the 1990-1991 Gulf War suffer from Gulf War Illness (GWI). Despite considerable research, effective treatments remain elusive. GWI refers to a complex of symptoms that typically include widespread chronic pain, persistent headache, memory and concentration problems, gastrointestinal difficulties, sleep disturbances and unexplained fatigue. This symptom profile is similar to that of fibromyalgia syndrome (FMS), a multi-symptom condition similar to GWI. Whereas, effective treatments for GWI have yet to be found, progress has been made in identifying medications to treat FMS. For example, the FDA has approved a number of medications including Duloxetine and Pregabalin for the treatment of FMS. Compared to placebo (PBO) Duloxetine (a serotonin norepinephrine reuptake inhibitor) and Pregabalin (an alpha-2-alpha-subunit calcium-channel ligand) significantly improved pain responses and fatigue. The capacity of Duloxetine to increase central levels of serotonin and norepinephrine as well as the more complex alterations of neurotransmitters and central nervous system (CNS) mediators of pain attributed to pregabalin are thought to be responsible for the medication's effects on pain, mood and sleep. Clinical practice and one open-label trial support the use of these medications in combination to achieve optimal symptom improvement amongst GWI sufferers; however, such combinations have not been formally tested in randomized controlled trials. The lack of progress in finding effective treatments for GWI, and the similarities between GWI and FMS, provides a rationale for determining if these FDA approved medications can provide significant symptomatic relief to Veterans who suffer from GWI. Central Texas is home to one of the highest number of Gulf War Veterans in the nation, thus the investigators' research team is ideally situated to conduct the proposed study. In a randomized, double-blind, controlled trial, 180 Veterans who meet defining criteria for GWI and whose symptom profile includes chronic widespread pain and sleep disturbances will be treated with one of the following medications; 1) AM Duloxetine+ PM placebo (PBO); 2) PM Pregabalin + AM PBO or 3) AM PBO + PM PBO. All active treatments will titrate from a lower dose in 2-week increments to the full therapeutic doses (FDA-approved for FMS). The outcome of the PBO double-dummy period will be compared statistically with 18 weeks of active therapy (weeks 5-22).
- Conditions
- Gulf War Illness
- Being tested
- Duloxetine, Pregabalin, Placebo
- Keywords
- Gulf War Illness, Pregabalin, Duloxetine, Gulf War Veterans, Cymbalta, Lyrica
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DuloxetineDrug
Also called Cymbalta
serotonin norepinephrine reuptake inhibitor
PregabalinDrug
Also called Lyrica
alpha-2-alpha subunit calcium channel ligand
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Active comparator | 60 mg of duloxetine in the AM for 20 weeks and placebo in PM Receives: Drug: Duloxetine; Drug: Placebo |
| Group 2 | Active comparator | 300 mg of pregabalin in the PM for 20 weeks and placebo in AM Receives: Drug: Pregabalin; Drug: Placebo |
| Group 3 | Placebo comparator | placebo in the AM \& PM for 20 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain by Likert Scale
Likert scale of pain rating
Measured: 120 days
Secondary outcomes (1)
Side Effects
Side effects checklist
Measured: Assessed every 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2013 (estimated)
- Study start24 Jun 2015
- Primary completion1 Aug 2019
- Study completion1 Aug 2019
Why it stopped: Terminated by Funder
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Gulf War IllnessStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Three arms comparing placebo to duloxetine and pregabalin
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 112 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Collaborators
- Texas A&M University
- Responsible party
- Sponsor
- Investigators
- Charles J Foulks, M.D., Study chair, Central Texas Veterans Health Care System, Temple, TX
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01846182
- Sponsor's protocol ID
- SPLD-016-12F
- Other IDs
- 6125
- Acronym
- REGIONS
- Status last verified
- Feb 2021
- First submitted
- 16 Apr 2013
- Last updated
- 12 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RCT of Duloxetine & Pregabalin for the Treatment of Gulf War Illness in Veterans
- ClinicalTrials.gov ID
- NCT01846182
- Acronym / sponsor ID
- REGIONS / SPLD-016-12F
- Conditions
- Gulf War Illness
- Keywords
- Gulf War Illness, Pregabalin, Duloxetine, Gulf War Veterans, Cymbalta, Lyrica
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated by Funder
- Enrolment
- 112 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Collaborators
- Texas A&M University
- Study start
- 24 Jun 2015 (actual)
- Primary completion
- 1 Aug 2019 (actual)
- Study completion
- 1 Aug 2019 (actual)
- First posted
- 3 May 2013 (estimated)
- Results
- Posted 12 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
At least 1 in 4 of the 700,000 U.S. Veterans who served in the 1990-1991 Gulf War suffer from Gulf War Illness (GWI). Despite considerable research, effective treatments remain elusive. GWI refers to a complex of symptoms that typically include widespread chronic pain, persistent headache, memory and concentration problems, gastrointestinal difficulties, sleep disturbances and unexplained fatigue. These symptoms are similar to that of fibromyalgia syndrome (FMS), another multi-symptom condition. Whereas, effective treatments for GWI have yet to be found, the FDA has approved duloxetine and pregabalin for the treatment of FMS. The lack of progress in finding effective treatments for GWI, and the similarities between GWI and FMS, provides a rationale for determining if these medications can provide relief to Veterans who suffer from GWI. This randomized controlled trial will test the efficacy of Duloxetine and Pregabalin for treating Gulf War Veterans who suffer from GWI.
Detailed description
At least 1 in 4 of the 700,000 U.S. Veterans who served in the 1990-1991 Gulf War suffer from Gulf War Illness (GWI). Despite considerable research, effective treatments remain elusive. GWI refers to a complex of symptoms that typically include widespread chronic pain, persistent headache, memory and concentration problems, gastrointestinal difficulties, sleep disturbances and unexplained fatigue. This symptom profile is similar to that of fibromyalgia syndrome (FMS), a multi-symptom condition similar to GWI. Whereas, effective treatments for GWI have yet to be found, progress has been made in identifying medications to treat FMS. For example, the FDA has approved a number of medications including Duloxetine and Pregabalin for the treatment of FMS. Compared to placebo (PBO) Duloxetine (a serotonin norepinephrine reuptake inhibitor) and Pregabalin (an alpha-2-alpha-subunit calcium-channel ligand) significantly improved pain responses and fatigue. The capacity of Duloxetine to increase central levels of serotonin and norepinephrine as well as the more complex alterations of neurotransmitters and central nervous system (CNS) mediators of pain attributed to pregabalin are thought to be responsible for the medication's effects on pain, mood and sleep. Clinical practice and one open-label trial support the use of these medications in combination to achieve optimal symptom improvement amongst GWI sufferers; however, such combinations have not been formally tested in randomized controlled trials. The lack of progress in finding effective treatments for GWI, and the similarities between GWI and FMS, provides a rationale for determining if these FDA approved medications can provide significant symptomatic relief to Veterans who suffer from GWI. Central Texas is home to one of the highest number of Gulf War Veterans in the nation, thus the investigators' research team is ideally situated to conduct the proposed study. In a randomized, double-blind, controlled trial, 180 Veterans who meet defining criteria for GWI and whose symptom profile includes chronic widespread pain and sleep disturbances will be treated with one of the following medications; 1) AM Duloxetine+ PM placebo (PBO); 2) PM Pregabalin + AM PBO or 3) AM PBO + PM PBO. All active treatments will titrate from a lower dose in 2-week increments to the full therapeutic doses (FDA-approved for FMS). The outcome of the PBO double-dummy period will be compared statistically with 18 weeks of active therapy (weeks 5-22).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Three arms comparing placebo to duloxetine and pregabalin
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Active comparator | Drug: Duloxetine, Drug: Placebo60 mg of duloxetine in the AM for 20 weeks and placebo in PM |
| Group 2 | Active comparator | Drug: Pregabalin, Drug: Placebo300 mg of pregabalin in the PM for 20 weeks and placebo in AM |
| Group 3 | Placebo comparator | Drug: Placeboplacebo in the AM \& PM for 20 weeks |
Who may qualify
- Ages
- 44 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Living in Central Texas near Killeen, Austin, Temple or Waco
- Served on active military duty and deployed to the Persian Gulf region for some period between August 1990 \& July 1991
- English speaking and able to understand the consent form and study questionnaires
- Willing to be randomized to treatment and participate in 1-month follow up
- men \& women between the ages of 43 to 70
Key exclusion criteria (16 listed)
- Unstable or poorly controlled chronic medical illness such as Diabetes type-II, Hypertension (HTN), heart disease, endocrine disorders, narrow angle glaucoma
- Significant Central Nervous System disease including transient ischemic attacks (TIAs) or stroke, Dementia, syncopal episodes, severe head trauma, multiple sclerosis
- Serious or advanced heart disease or clinically relevant abnormal electrocardiogram (ECG), postural hypotension
- Untreated sleep apnea or body mass index placing patients at risk for undiagnosed sleep apnea (BMI> 35 kg/m2)
- Diabetes type-I and patients with Diabetes type-II associated with peripheral neuropathy, hepatitis, liver failure/cirrhosis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DuloxetineAlso: Cymbaltaserotonin norepinephrine reuptake inhibitor | Drug | Group 1 |
| PregabalinAlso: Lyricaalpha-2-alpha subunit calcium channel ligand | Drug | Group 2 |
| PlaceboPlacebo | Drug | Group 1, Group 2, Group 3 |
Primary outcome
Pain by Likert Scale
Time frame: 120 days
Likert scale of pain rating
1 secondary outcome
Side Effects
Time frame: Assessed every 2 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Gulf War Illness
RecruitingObservational study
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Ca-Mg Butyrate in Gulf War Illness
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Mechanisms of Gulf War Illness
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Charles J Foulks, M.D. study chair
Central Texas Veterans Health Care System, Temple, TX
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Duloxetine and Pregabalin in people with Gulf War Illness, run by VA Office of Research and Development at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pain by Likert Scale (time frame: 120 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2021.