Effects of Riluzole on CNS Glutamate and Fatigue in Breast Cancer Survivors With High Inflammation
| Status: | Recruiting |
|---|---|
| Conditions: | Breast Cancer, Other Indications |
| Therapuetic Areas: | Oncology, Other |
| Healthy: | No |
| Age Range: | 21 - 65 |
| Updated: | 6/9/2018 |
| Start Date: | April 2016 |
| End Date: | November 2019 |
| Contact: | Andrew H Miller, MD |
| Email: | amill02@emory.edu |
| Phone: | 404-727-8260 |
The goal of the proposed research is to determine whether riluzole, a drug that increases
glutamate reuptake, will decrease CNS glutamate in breast cancer survivors with increased
inflammation and fatigue. We 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, we 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). Patients 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.
glutamate reuptake, will decrease CNS glutamate in breast cancer survivors with increased
inflammation and fatigue. We 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, we 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). Patients 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.
The primary objective of the proposed research 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.
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.
Inclusion Criteria:
- Must have completed surgery for Stage I-III breast cancer (lumpectomy or mastectomy)
with or without neoadjuvant or adjuvant chemotherapy and with or without radiation.
- Must be 1-3 years post-treatment for breast cancer
- Must have a plasma c-reactive protein (CRP) level of >3mg/L
- Must have a score of ≥4 (out of 10 points, 0 being no fatigue and 10 being severe,
incapacitating fatigue) on a Single Item Screening Scale for Fatigue
Exclusion Criteria:
- Presence of a medical condition that might represent a risk for riluzole treatment,
including history of allergic reaction to riluzole and evidence of liver disease
- Presence of a medical condition that might potentially confound the relationship among
CNS glutamate, inflammation and behavior/cognition, including autoimmune or
inflammatory disorders, chronic infectious diseases (e.g. HIV, hepatitis B or C),
pregnancy, neurologic disorders (including a history of serious head trauma or
seizures), liver disease (as manifested as an elevation in liver transaminases) and
uncontrolled cardiovascular, metabolic, pulmonary or renal disease (as determined by
medical history and laboratory testing)
- Current or past history of schizophrenia
- Individuals with bipolar disorder who have experienced a manic episode within 6 months
of study entry, or at the discretion of the study doctor
- Individuals receiving antidepressants, mood stabilizers, antipsychotic medications or
benzodiazepines or drugs known to affect the immune system (e.g. glucocorticoids,
methotrexate), or at the discretion of the study doctor
- Individuals exhibiting signs of infection at the screening visit will be rescheduled
to screen when symptoms have resolved
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