Jun 02, 2008

Low Dose Naltrexone Update

We have received a number of inquiries about the use of low dose naltrexone (LDN) as a treatment for multiple sclerosis. There are very limited data from controlled clinical trials to support the use of naltrexone in multiple sclerosis (MS). Further study is needed to determine if this is a safe and effective treatment for people with MS.

Naltrexone is an opioid antagonist that has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of addictions to opioids and alcohol. At significantly lower doses, it has been prescribed as a treatment for a variety of diseases, including various types of cancers, HIV/AIDS, Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), emphysema, as well as MS and other autoimmune diseases.

Studies in Other Diseases

In an open-label pilot study of LDN for people with irritable bowel syndrome, (Kariv R et al., Digestive Diseases and Sciences 2006;51(12):2128-33), those receiving LDN experienced a greater number of pain-free days.

In another open-label, pilot study (Smith JP et al., American Journal of Gastroenterology; 2007 102(4): 820-8) designed to evaluate the safety and efficacy of LDN in Crohn’s disease, patients experienced a significant reduction in disease activity and improvement in quality of life. The findings from this study led to funding by NIH for a Phase II clinical trial of LDN in Crohn’s disease.

To date, there have been no published studies of LDN in other diseases.

Studies in MS

In an article by Yash Agrawal, MD, PhD, (Med Hypotheses 2005; 64(4):721-4), Dr. Agrawal hypothesizes that LDN reduces injury to the nervous system by decreasing the harmful effects of two classes of chemicals, “free radicals” and “excitotoxins. He urged that clinical trials be conducted as soon as possible to determine if the proposed mechanism of action is a safe and effective treatment for MS.

As an initial step, the Society funded a pilot study by Ian Zagon, PhD, from the College of Medicine at Pennsylvania State University, looking at the effects of both low- and high-dose naltrexone in mice with the MS-like disease, EAE. Based on earlier findings that opioids (which occur naturally on cells in the nervous system) may regulate immunity, wound healing, and cell renewal, Zagon and his colleagues are looking to see if mice treated with naltrexone demonstrate any changes in their MS-like symptoms or underlying disease activity.

We are pleased to announce that human trials in LDN are underway as well:

• Dr. Gianvito Martino (San Raffaele Hospital, Milan, Italy) and colleagues presented an abstract of their trial of LDN at the 2008 Academy of Neurology (AAN) meeting. They administered 5 mg of LDN to 40 people with primary-progressive MS for 6 months, evaluating its safety and effects on spasticity, pain and fatigue. Five patients dropped out. Significant improvements were shown in fatigue and depression. Transient increases in liver enzymes, urinary tract infections, mild agitation and sleep disturbance were the most common adverse events.
• Dr. Bruce Cree (University of California, San Francisco) and colleagues reported at the AAN that eight weeks of treatment with LDN significantly improved quality of life (specifically, mental health, pain, and self-reported cognitive function) in 60 people with MS as measured by the MS Quality of Life Inventory. No impact was observed on physical quality of life (such as fatigue, bowel and bladder control, sexual satisfaction, and visual function). Vivid dreaming was reported during the first week of treatment by some patients, but no other adverse effects were reported. Patient advocates with MS have funded Dr. Cree to conduct a larger, controlled study that will involve 80 people with MS.
• TheMindBrain Consortiumand the Department of Psychiatry of Summa Hospital System of Akron, Ohio—together with the Oak Clinic for the Treatment of Multiple Sclerosis—are conducting a 16-week, double-blind, randomized, placebo-controlled, crossover-design analysis of 36 patients with either progressive or relapsing-remitting MS. The study, under the direction of Dr. David Pincus, is examining symptom severity as well as any changes in quality of life, sleep patterns, and affective (emotional) states. Results are expected in the summer of 2008.

As stated on the National MS Society Web site, the Society is open to considering any high quality and relevant research protocol. Any agent that has the potential to safely and effectively treat MS is of interest to the Society.

In collaboration with Allen Bowling, MD, PhD