Progression of intervention-focused research for Gulf War illness - Review Chester et al Oct 2019

[Sly Saint]

Abstract

The Persian Gulf War of 1990 to 1991 involved the deployment of nearly 700,000 American troops to the Middle East. Deployment-related exposures to toxic substances such as pesticides, nerve agents, pyridostigmine bromide (PB), smoke from burning oil wells, and petrochemicals may have contributed to medical illness in as many as 250,000 of those American troops. The cluster of chronic symptoms, now referred to as Gulf War Illness (GWI), has been studied by many researchers over the past two decades. Although over $500 million has been spent on GWI research, to date, no cures or condition-specific treatments have been discovered, and the exact pathophysiology remains elusive.

Using the 2007 National Institute of Health (NIH) Roadmap for Medical Research model as a reference framework, we reviewed studies of interventions involving GWI patients to assess the progress of treatment-related GWI research. All GWI clinical trial studies reviewed involved investigations of existing interventions that have shown efficacy in other diseases with analogous symptoms. After reviewing the published and ongoing registered clinical trials for cognitive-behavioral therapy, exercise therapy, acupuncture, coenzyme Q10, mifepristone, and carnosine in GWI patients, we identified only four treatments (cognitive-behavioral therapy, exercise therapy, CoQ10, and mifepristone) that have progressed beyond a phase II trial.

We conclude that progress in the scientific study of therapies for GWI has not followed the NIH Roadmap for Medical Research model. Establishment of a standard case definition, prioritized GWI research funding for the characterization of the pathophysiology of the condition, and rapid replication and adaptation of early phase, single site clinical trials could substantially advance research progress and treatment discovery for this condition.

https://link.springer.com/article/10.1186/s40779-019-0221-x

GWI is a phenomenon that falls under the umbrella of the broader set of conditions termed chronic multisymptom illness (CMI). CMI has been defined by the Institute of Medicine (IOM) as a cluster of medically unexplained, chronic symptoms that can include fatigue, headaches, joint pain, indigestion, insomnia, dizziness, respiratory disorders, and memory problems [8]. In addition to GWI, other types of CMI include myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), and irritable bowel syndrome (IBS).

 

[Sly Saint]

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All GWI clinical trial studies reviewed involved investigations of existing interventions that have shown efficacy in other diseases with analogous symptoms. After reviewing the published and ongoing registered clinical trials for cognitive-behavioral therapy, exercise therapy, acupuncture, coenzyme Q10, mifepristone, and carnosine in GWI patients, we identified only four treatments (cognitive-behavioral therapy, exercise therapy, CoQ10, and mifepristone) that have progressed beyond a phase II trial.

Cognitive behavioral therapy
Description of the intervention
Cognitive Behavioral Therapy (CBT) is a combination psychotherapy in which patients identify and correct maladaptive beliefs (the cognitive component) and utilize thought exercises or concrete actions (the behavioral component) to reduce symptoms and improve functioning [49]. In general, CBT is intended for ongoing, long-term use outside of the therapeutic setting after the specific skills are mastered with a therapist. CBT is an accepted, evidence-based treatment for many disorders, from mood and anxiety disorders (such as depression, panic disorder, and obsessive-compulsive disorder) to insomnia, substance cessation, and pain management.

History of the intervention
By the late 1990s, CBT had been evaluated in treating ME/CFS and chronic pain syndromes, and it had been found to be efficacious in improving the symptoms and functional status in individuals with these conditions. One randomized clinical trial in 1996 evaluating the efficacy of adding CBT to the medical care of patients with CFS found that 73% of patients receiving CBT in addition to medical care achieved an improvement in functioning (change in Karnofky score by 10 points or more) compared to 27% of patients receiving only medical care (difference of 47% points; 95% CI 24–69) [50]. Another randomized clinical trial in 1997 comparing the efficacy of CBT and relaxation therapy in treating CFS found that 70% of the completers in the cognitive-behavioral therapy group achieved good outcomes (substantial improvement in physical functioning) compared with 19% of those in the relaxation group who completed treatment [51].

Exercise therapy
Description of the intervention
Exercise, a structured and focused form of physical activity, has long been known to confer significant health benefits for many organ systems and in patients with many different illnesses [57]. Research has identified specific, efficacious exercise prescriptions based on age, health status, gender, body habitus, disease/condition, and other factors.

History of the intervention
Exercise has been shown to be an effective treatment for improving the symptoms of CMI. Peters et al. performed a randomized controlled trial of 228 patients with medically unexplained symptoms, which showed that using aerobic exercise, in comparison to non-aerobic stretching, for 1 hour twice a week for 10 weeks, improved functional outcomes for patients.