Effects of Riluzole on CNS Glutamate and Fatigue in Breast Cancer Survivors With High Inflammation
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|ClinicalTrials.gov Identifier: NCT02796755|
Recruitment Status : Completed
First Posted : June 13, 2016
Results First Posted : April 14, 2021
Last Update Posted : April 14, 2021
|Condition or disease||Intervention/treatment||Phase|
|Inflammation Fatigue||Drug: Riluzole Drug: Placebo||Phase 4|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||30 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Effects of Riluzole on CNS Glutamate and Fatigue in Breast Cancer Survivors With High Inflammation|
|Study Start Date :||April 2016|
|Actual Primary Completion Date :||October 24, 2019|
|Actual Study Completion Date :||October 24, 2019|
Experimental: Riluzole Arm
Participants will take a daily oral dose of 100 mg of riluzole (50 mg two times per day). Participants will be instructed to take the study medication on an empty stomach (1 hour before or 2 hours after meals).
Study participants randomized to this arm will take 100 mg/day of riluzole for 8 weeks.
Other Name: Rilutek
Placebo Comparator: Placebo Arm
Participants will take a daily oral dose of 100 mg of a placebo that appears identical to riluzole (50 mg two times per day). Participants will be instructed to take the study medication on an empty stomach (1 hour before or 2 hours after meals).
Study participants randomized to this arm will take a placebo, that matches the appearance of 100 mg tablets of riluzole, daily for 8 weeks.
- Central Nervous System (CNS) Glutamate Measured by Magnetic Resonance Spectroscopy (MRS) [ Time Frame: Baseline, Week 1, Week 8 ]Magnetic resonance spectroscopy (MRS) is a specialized technique associated with magnetic resonance imaging (MRI). MRS is a non-invasive way to obtain biochemical information about the tissues of the human body. Participants underwent single voxel (3-dimensional volume X pixel) MRS to measure CNS glutamate before and after 1 and 8 weeks of riluzole or placebo treatment. Voxels were placed in the right and left basal ganglia and the dorsal anterior cingulate cortex (dACC), well known targets of inflammatory cytokines on the brain, and cytokine effects on these brain regions have been associated with symptoms of fatigue and cognitive dysfunction as well as reduced motivation. MRS has shown that chronic exposure to the inflammatory cytokine interferon (IFN)-alpha leads to increased CNS glutamate (as reflected by the glutamate/creatine (Glu/Cr) ratio) which correlated with symptoms of fatigue and cognitive dysfunction.
- Multidimensional Fatigue Inventory (MFI) Score [ Time Frame: Baseline, Weeks 1, 2, 4, 8 ]The Multidimensional Fatigue Inventory (MFI) is a 20-item scale used to evaluate the presence and severity of fatigue among subjects by self-reports. The MFI assesses 5 dimensions of fatigue, including general fatigue, physical fatigue, mental fatigue, reduced activity, and reduced motivation. Participants respond to fatigue related statements using a 5 point scale where 1 = "yes, that is true" and 5 = "no, that is not true". Total scores range from 20 to 100 and higher scores indicate greater fatigue.
- Patient-Reported Outcomes Measurement Information System (PROMIS) - Fatigue Short Form Score [ Time Frame: Baseline, Weeks 1, 2, 4, 8 ]PROMIS-Fatigue Short Form is a 7-item scale developed by the Patient-Reported Outcome Measurement Information System (PROMIS), a part of the NIH Roadmap Initiative which is focused on developing a publicly available resource of standardized, accurate, and efficient outcome measures of symptoms, distress, and functioning. The criterion for a minimally clinically important difference in patients with advanced-stage cancer is a 3 to 5 point difference in raw score. Recommendations for high priority research on cancer-related fatigue recommend use of the PROMIS fatigue scale to allow comparison of results across studies. Respondents indicate how much they agree with the item statements on a scale from 1 (not at all) to 5 (very much). Total scores range from 7 to 35 with higher scores indicating greater fatigue.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02796755
|United States, Georgia|
|Emory University Winship Cancer Institute|
|Atlanta, Georgia, United States, 30322|
|Principal Investigator:||Andrew H Miller, MD||Emory University|