Effects of Riluzole on CNS Glutamate and Fatigue in Breast Cancer Survivors With High Inflammation
Condition: Inflammation; Fatigue
MeSH terms: Inflammation; Fatigue
Study type: Interventional
Phase: Phase 4

Summary: 
      The goal of the proposed research is to determine whether riluzole, a drug that increases
      glutamate reuptake, will decrease central nervous system (CNS) glutamate in breast cancer
      survivors with increased inflammation and fatigue. The researchers will also determine
      whether decreasing glutamate with riluzole will reverse inflammation-related fatigue and
      other symptoms including cognitive dysfunction and decreased motivation. To accomplish these
      goals, the researchers plan to conduct an 8 week, double-blind, randomized control trial of
      riluzole (100 mg/d) versus placebo in 40 breast cancer survivors (n=20 per group). All breast
      cancer survivors will have completed treatment within 1-3 years and have a fatigue level of
      ≥4 (on a 10 point scale) and a plasma c-reactive protein (CRP) concentration >3mg/L
      (indicative of high inflammation). Participants will undergo magnetic resonance spectroscopy
      (MRS) to measure CNS glutamate before and after 2 and 8 weeks of riluzole or placebo
      treatment. Fatigue and other behavioral assessments including measures of cognitive function
      and motivation will be conducted before and after treatment and correlated with the change in
      CNS glutamate.
    

Detailed description: 
      Breast cancer is one of the most common cancers among women with ~250,000 new cases diagnosed
      in the US each year. Significant advances have been made in treating breast cancer, and the
      current number of women in the US who are considered breast cancer survivors is over 2
      million. Despite these advances, breast cancer and its treatment comes at a considerable cost
      for a significant percentage of women with up to 30% of women experiencing behavioral and/or
      cognitive symptoms months to years after treatment completion. The mechanisms which
      contribute to these symptoms are only beginning to be understood, however, mounting data
      suggest that inflammation may be involved.

      Prior research has demonstrated significant relationships between inflammatory markers and
      inflammatory signaling pathways and symptoms of fatigue and cognitive dysfunction in patients
      with multiple forms of cancer including breast cancer. There are a number of theories as to
      how inflammation may influence fatigue and cognition function in breast cancer patients. One
      neurotransmitter pathway that may be involved is glutamate. Inflammatory cytokines have been
      shown to decrease glutamate reuptake and increase glutamate release from astrocytes.

      The primary objective of this study is to provide the first data on the role of CNS glutamate
      and symptoms of fatigue in breast cancer patients using MRS and a medication that has been
      shown to lower CNS glutamate in animal models and human subjects. No previous study has
      examined the potential connection between increased inflammation, increased CNS glutamate and
      symptoms in breast cancer patients, although there is strong clinical and preclinical support
      for an important interrelationship among these variables. Identification of a significant
      relationship between increased CNS glutamate and symptoms will:

        -  Enable the development of inflammatory biomarkers to identify patients with altered CNS
           glutamate.

        -  Help focus future studies using glutamate stabilizing medications and glutamate
           antagonists on patients most likely to respond to glutamate-targeted therapies
           (personalization of trials and treatment).

        -  Expand treatment studies to include synergistic or sequential targeting of inflammation
           and glutamate to reduce symptom burden in breast cancer patients.

      This study will also serve as a foundation for efforts to link the impact of inflammatory
      cytokines and their relationship with increased CNS glutamate and behavior to a variety of
      cancers. Moreover, by testing novel treatment approaches (targeting glutamate), this study
      may ultimately improve the quality of life of breast cancer and other cancer patients.
    

Intervention name(s): Riluzole; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Study participants randomized to this arm will take 100 mg/day of riluzole for 8 weeks.; Study participants randomized to this arm will take a placebo, that matches the appearance of 100 mg tablets of riluzole, daily for 8 weeks.
Other intervention name(s): Rilutek
Intervention MeSH terms: Riluzole
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Central Nervous System (CNS) Glutamate; Breast Cancer Treatment; Fatigue; Cognitive Dysfunction; Behavioral; Psychometrics; Imaging Technology; Magnetic Resonance Spectroscopy