Chronic Fatigue Syndrome/Fibromyalgia

Chronic Fatigue Syndrome (CFS) is a common condition in Canada and North America. There are an estimated 30,000 Canadians with CFS , 442,200 Canadians with Fibromyalgia - and this is an underestimate. The cause of CSF/Fibromyalgia is unknown, but there are elements of these syndromes that suggest they may be of viral origin. Most commonly it is believed that a member of the herpes virus family – Epstein-Barr Virus (EBV) - is a possible cause, although this has not been consistently found to be the cause. It is possible that these syndromes could be the result of different viruses making the specific etiology of CFS/Fibromyalgia difficult to determine.

Some patients with CFS/Fibromyalgia have evidence of a chronic viral infection as measured by a cytokine profile and markers of increased endogenous interferon production. They include elevated levels of interleukin tumor necrosis factor – alpha (TNF-ALPHA), increased O-A2’-5’ synthetase, IL-4, and IL-15.

This suggests there is an inflammatory response and likely oxidative stress accompanying this inflammatory response. Natural products – nutraceuticals could be used to decrease the oxidative stress in these patients and this may decrease their symptoms, although there is no claim of an antiviral effect. At NRG we are committed to advancing these nutraceutical based theories and protocols.

Chronic Liver Disease in the form of HBV and HCV

Currently there are more than 670 million people globally suffering from chronic liver disease in the form of Hepatitis B or C. Viral hepatitis accounts for significant morbidity and mortality from chronic infection worldwide. There are an estimated 170 million to 200 million patients with chronic hepatitis C infection, and an estimated 360 million to 400 million chronic carriers of hepatitis B. These are two very distinct viruses that have different mechanisms of replication and are susceptible to different antiviral agents. Chronic hepatitis B infection can lead to cirrhosis or hepatocellular carcinoma. Hepatitis B is one of the most common causes of fatal cancer in the world. Chronic hepatitis C infection can also lead to cirrhosis, end-stage liver disease, and hepatocellular carcinoma (HCC). There are an estimated 600,000 – 700,00 people that die from cirrhosis due to HCV infection, and an additional 500,000 that will die from HCC from HBV or HCV. In North America and western Europe hepatitis C is the most common cause of end-stage liver disease resulting in liver transplantation. The current treatment for hepatitis C is pegylated interferon and ribavirin. However, 100% of patients with hepatitis C virus who undergo liver transplantation will suffer re-infection of their transplanted liver and therapy with pegylated interferon and ribavirin is less effective after transplantation.

The focus of both of these studies will be to prove that either of these diseases are inflammatory based and by reversing inflammation we can slow or even stop disease progression at a cellular level which will hopefully return quality of life to those affected by either of these diseases.

Clinical Trial

If the pilot study shows benefit, it would be followed by a double-blind, placebo-controlled study. This larger study may require multiple sites to accumulate the numbers rapidly and would require a significant number of patients in each arm – 30 placebo/30 treatment would be the minimal numbers. This type of study would be done with appropriate financing and would be at least 12-18 months away.

Pilot Study

Select 5 patients with classical symptoms of the CFS. Determine cytokine levels and markers of interferon activation in these patients (objective measurements). Treat with the appropriately selected nutraceuticals and monitor the clinical response (subjective), measure “quality of life” at baseline and after 6 months. Objective measurement of cytokines – pre-treatment and at 3 and 6 months on therapy.

Clinical Trial

If the pilot study suggests that these patients would benefit from this treatment, then a placebo-controlled double-blind study would be designed. This study would include a minimum of 60 patients with 30 receiving the treatment and 30 on placebo treatment. This would involve the CFS Society of Alberta and Dr. Klein in Calgary. Patients would have to be carefully selected to meet the entry criteria. Since the nutraceuticals being used would be directed as anti-oxidative stress agents, all patients entering the study would have to have elevated cytokines or markers of interferon stimulation. To do this study, the cytokine assays would be done at a reference laboratory (e.g. Redpath) or we would need to set up the assays in house. In either case, the study would be 18-24 months downstream and would be expensive to complete – after sales of NRG have reached its projected targets.

Currently Nutraceutical Research Group is committed to advancing clinical research in these areas under the direction of Dr. Lorne Tyrrell at the University of Alberta.

Non-invasive Assessment of Liver Fibrosis by measurement of stiffness in patients with chronic hepatitis C

Liver fibrosis is the main predictor of the progression of chronic hepatitis C, and its assessment by liver biopsy (LB) can help determine therapy. However, biopsy is an invasive procedure with several limitations. A new, non-invasive medical device based on transient elastography has been designed to measure liver stiffness. The aim of this study was to investigate the use of liver stiffness measurement (LSM) in the evaluation of liver fibrosis in patients with chronic hepatitis C.

We prospectively enrolled 327 patients with chronic hepatitis C in amulticenter study. Patients underwent LB and LSM.METAVIR liver fibrosis stages were assessed on biopsy specimens by 2 pathologists. LSM was performed by transient elastography. Efficiency of LSM and optimal cutoff values for fibrosis stage assessment were determined by a receiver-operating characteristics (ROC) curve analysis and cross-validated by the jack-knife method. LSM was well correlated with fibrosis stage (Kendall correlation coefficient: 0.55; P<.0001).

The areas underROCcurves were 0.79 (95% CI, 0.73-0.84) for F > 2, 0.91 (0.87-0.96) for F > 3, and 0.97 (0.93-1) for F _ 4; for larger biopsies, these values were, respectively, 0.81, 0.95, and 0.99. Optimal stiffness cutoff values of 8.7 and 14.5 kPa showed F > 2 and F _ 4, respectively. In conclusion, noninvasive assessment of liver stiffness with transient elastography appears as a reliable tool to detect significant fibrosis or cirrhosis in patients with chronic hepatitis C…read more