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Research Examining Gulf War Illness in Our Nations Service Members (REGIONS)

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ClinicalTrials.gov Identifier: NCT01846182
Recruitment Status : Recruiting
First Posted : May 3, 2013
Last Update Posted : September 6, 2017
Sponsor:
Collaborators:
Information provided by (Responsible Party):

Study Description
Brief 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. 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.

Condition or disease Intervention/treatment Phase
Gulf War Illness Drug: Duloxetine Drug: Pregabalin Drug: Placebo Phase 2

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

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: RCT of Duloxetine & Pregabalin for the Treatment of Gulf War Illness in Veterans
Actual Study Start Date : June 24, 2015
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : January 1, 2021

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Active Comparator: Group 1
60 mg of duloxetine in the AM for 20 weeks
Drug: Duloxetine
serotonin norepinephrine reuptake inhibitor
Other Name: Cymbalta
Drug: Placebo
Placebo
Active Comparator: Group 2
300 mg of pregabalin in the PM for 20 weeks
Drug: Pregabalin
alpha-2-alpha subunit calcium channel ligand
Other Name: Lyrica
Drug: Placebo
Placebo
Placebo Comparator: Group 3
placebo in the AM & PM for 20 weeks
Drug: Placebo
Placebo


Outcome Measures

Primary Outcome Measures :
  1. Pain , Safety, tolerability [ Time Frame: Assessed every 2 weeks up to 34 weeks ]
    Pain as measured by a 10-point Visual Analog scale Physical component of the short form-36 (SF-36) (Veteran version) Side Effects Check list


Secondary Outcome Measures :
  1. Side Effects [ Time Frame: Assessed every 2 weeks ]
    Side effects checklist


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   44 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.]

Exclusion Criteria:

  • 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
  • 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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01846182


Contacts
Contact: Dena Davidson, PhD (254) 297-5169 Dena.Davidson@va.gov
Contact: Peggy J Pazzaglia, MD (254) 624-5765 Peggy.Pazzaglia@va.gov

Locations
United States, Texas
Central Texas Veterans Health Care System, Temple, TX Recruiting
Temple, Texas, United States, 76504
Contact: Christine A Kuhn, MSN BSN    254-297-3954    Christine.Kuhn@va.gov   
Contact: Randy Tea, MA    (254) 297-3950    Randy.Tea@va.gov   
Principal Investigator: Dena Davidson, PhD         
Central Texas Veterans Health Care System Waco VA Medical Center, Waco, TX Recruiting
Waco, Texas, United States, 76711
Contact: Dena Davidson, PhD    254-297-5169    Dena.Davidson@va.gov   
Sponsors and Collaborators
VA Office of Research and Development
Texas A&M University
Baylor University
Investigators
Principal Investigator: Dena Davidson, PhD Central Texas Veterans Health Care System, Temple, TX
More Information

Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT01846182     History of Changes
Other Study ID Numbers: SPLD-016-12F
6125 ( Other Identifier: Clinical Science Research & Development )
First Posted: May 3, 2013    Key Record Dates
Last Update Posted: September 6, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by VA Office of Research and Development:
Gulf War Illness
Pregabalin
Duloxetine
Gulf War Veterans
Cymbalta
Lyrica

Additional relevant MeSH terms:
Pregabalin
Duloxetine Hydrochloride
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anticonvulsants
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Serotonin and Noradrenaline Reuptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Antidepressive Agents
Dopamine Agents