Trial of Naltrexone and Dextromethorphan for Gulf War Illness (GWI Treatment)

Trial of Naltrexone and Dextromethorphan for Gulf War Veterans Illnesses

Veterans of the 1991 Gulf War who developed Gulf War Illness are being studied. Treatments with FDA approved generic drugs are being administered to see if they help with the symptoms of Gulf War Illness, such as chronic fatigue; difficulty with memory, concentration, and thinking; widespread chronic pain; and autonimic dysfunction. Drugs to be tested are dextromethorphan and naltrexone.

Study Overview

• Status: Completed
• Conditions: Gulf War Illness
• Intervention / Treatment: Drug: naltrexone; Drug: Dextromethorphan

Detailed Description

Gulf war veterans' illnesses comprise distinct clusters of symptom-defined illnesses for which there are neither diagnostic tests nor effective treatments. Gulf war veterans had variable exposures to a number of chemicals, including organophosphate insecticides, pyrethrum-related insecticides, DEET, Pyridostigmine bromide, smoke from oil well fires, and Sarin gas. Gulf war veterans' illnesses may reflect an inflammatory cycle involving the brain which may be a common mechanism of many neurological conditions, whether initiated by toxic exposures, infection, or trauma. In this theory, central nervous system inflammation initiated by toxic exposures and sometimes exacerbated by subsequent exposures is a component of illness hypothesized to explain the neurological manifestations. Substance P release at sensory nerve endings is an explanation for the peripheral pain manifestations of illness.

This theory suggests that novel anti-inflammatory drugs may be of benefit in symptom-defined illnesses related to a cycle of inflammation. Dr. J. S. Hong's laboratory at the National Institute of Environmental Health Sciences has demonstrated that Morphine-related analogs, including Naltrexone and Dextromethorphan, have great potency in anti-inflammation and neuroprotective effects. Naltrexone is a safe and readily available generic medication. Dextromethorphan is also a safe and readily available generic medication that is available without a prescription as a cough medication. Results from several clinical trials showed that Naltrexone is effective in several inflammation-related diseases, such as neurogenic pain, movement disorders, etc. In addition, there were no obvious side effects in patients taking this drug for six months. This project will conduct randomized double-blinded studies for treating ill Gulf war veterans with Naltrexone and Dextromethorphan. Laboratory tests for markers of inflammation including neurogenic inflammation will be performed pre- and post-treatment, to see if these markers are elevated and if so, to see if treatment modulates these markers.

Ill Gulf veterans will be recruited through the media, veterans groups, and individual veteran activists. A screening telephone interview will be performed to determine if the veterans meet a modified Kansas case definition for inclusion. Those veterans who meet study criteria will be invited to participate. Eligible veterans will be invited for an initial visit that will consist of obtaining written informed consent, a medical history, physical examination, and laboratory testing. Institutional review board approval of the study will be in place. The pharmacy staff at the institution will prepare the medications and placebo in identical capsules.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Brody School of Medicine a East Carolina Univesity

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Served in the Gulf War and developed the symptoms of Gulf War Illness as described by the modified Kansas Case Definition

Exclusion Criteria:

• Pregnant women, nursing mothers, individuals requiring medications that have drug interactions with dextromethorphan or naltrexone, cancer not in remission, chronic infectious disease, liver disease, lupus, multiple sclerosis, stroke, under current treatment for schizophrenia, bipolar disorder/manic depression, and depression.
• Those with a history of current illicit drug use will be excluded. Individuals who have had recent surgery will not be enrolled until they have completely recovered from the surgery.
• Subjects participating in other clinical trials will be excluded.
• Those enrolled recently in a clinical trial will be enrolled after a washout period of one month.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Naltrexone Study Drug; Subjects will take naltrexone 4.5 mg daily for three months.	Drug: naltrexone; Randomized controlled trial of naltrexone for Gulf War Illness.
Placebo Comparator: Naltrexone placebo; Subjects will take a 3 month course of a placebo pill identical in appearance to the naltrexone study drug.	Drug: naltrexone; Randomized controlled trial of naltrexone for Gulf War Illness.
Active Comparator: dextromethrophan study drug; subjects will take a sustained release dextromethorphan pill twice a day.	Drug: Dextromethorphan; Randomized controlled trial of dextromethorphan for Gulf War Illness
Placebo Comparator: dextromethoprhan placebo; Subjects will take a 3 month course of a placebo pill identical in appearance to the dextromethorphan study drug.	Drug: Dextromethorphan; Randomized controlled trial of dextromethorphan for Gulf War Illness

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptoms Scores	Symptoms of Gulf War Illness will be scored by participants using a ten center meter scale. Scores will be collected at the end of 12 weeks/16 weeks/28weeks	28 weeks approximately

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SF-36	Subjects will complete a standard health assessment tool, the SF-36, at the end of each course of therapy. Scores will be collected at 12 weeks/16 weeks/28 weeks	28 weeks approximately
Connors Continuous Performance Test	Subjects will take the Connors Continuous Performance Test at the end of each course of study drug or placebo. Scores will be collected at 12 weeks/16 weeks/28 weeks	28 weeks approximately

Collaborators and Investigators

• Sponsor: East Carolina University

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: August 24, 2012
• First Submitted That Met QC Criteria: July 31, 2014
• First Posted (Estimate): August 1, 2014

Study Record Updates

• Last Update Posted (Estimate): March 3, 2016
• Last Update Submitted That Met QC Criteria: March 2, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: treatment; Gulf War Illness; naltrexone; dextromethorphan
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Sensory System Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Narcotic Antagonists; Respiratory System Agents; Alcohol Deterrents; Antitussive Agents; Naltrexone; Dextromethorphan
• Other Study ID Numbers: 090562