Randomized Controlled Trial of Naltrexone & Dextromethorphan for Gulf War Vetera Grant uri icon

abstract

  • Background: Armed services personnel in the 1991 Gulf War were exposed to a complex mixture of chemicals, including organophosphate insecticides, smoke from oil well fires, fuel oil, sarin gas, DEET, pyrethrums, and pyridostigmine bromide. Approximately 15% became chronically ill with symptom based and neuropsychiatric illnesses. Conventional medical practice has little too offer the ill veterans of the Gulf War. Morphanans have demonstrated neuro-protective effects in animal models and might provide symptomatic relief to ill gulf war veterans. Objective/Hypothesis: The hypothesis to be tested is that ill gulf war veterans can be treated with the morphanans naltrexone and dextromethorphan. The objective of this study is to conduct a placebo-controlled double-blinded study of naltrexone and dextromethorphan in ill gulf war veterans. Specific aims: The specific aims of this project are to determine the efficacy of naltrexone and dextromethrophan in treating ill gulf war veterans, and to determine if inflammatory markers including markers of neuro-inflammation are elevated in these veterans and affected by treatment. Study design: A placebo-controlled double-blinded cross-over design will be used to determine the efficacy of naltrexone and dextromethorphan in providing symptomatic relief of ill gulf war veterans. Enrolled veterans will receive three four week courses of therapy: placebo, naltrexone 4.5 mg/day, and dextromethorphan 30 mg/day, separated by two week washout periods. At the beginning and end of each course of therapy veterans will be assessed with a medical history and physical examination. Symptom scores will be monitored using SF?36, the Clinical Global Impression Scale, and visual analogue symptom scales. The appropriate control will be placebo. Eligibility for participation will be determined by the Kansas definition of ill gulf war veterans. At the beginning and end of each course of therapy, phlebotomy will be performed with serum samples frozen at -70 degrees Celsius for assays of pro-inflammatory cytokines and markers of neurogenic inflammation using immunoassays [Luminox and ELIZA]. Statistical analysis will be performed to determine changes in symptom scores with each course of therapy. Values of pro-inflammatory cytokines and markers of neurogenic inflammation will be compared pre- and post- courses of therapy, with baseline values compared to age and sex matched healthy controls. Impact: This study will have to power to determine if dextromethorphan and naltrexone are efficacious in relieving symptoms in ill gulf war veterans. If the treatments are successful, there will be a safe and inexpensive treatment available to the veterans. A secondary impact will be to determine if pro-inflammatory cytokines and markers of neurogenic inflammation are elevated in the veterans. If one or more of these markers are elevated, there will be the two-fold benefit of having a biomarker of disease and insight into the mechanism.

date/time interval

  • July 2010 - June 2014

contributor