InflammationPhase 4NCT02796755
Effects of Riluzole on CNS Glutamate and Fatigue in Breast Cancer Survivors With High Inflammation
A Phase 4 study testing Riluzole in people with Inflammation and Fatigue, run by Emory University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 65 years, women only
- Conditions the study is for
- Inflammation, Fatigue
- What is being tested?
- Riluzole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2016to 24 Oct 2019
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 1-5 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Emory University Winship Cancer Institute
Atlanta, Georgia, 30322
About this study
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.
Read the 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.
- Conditions
- Inflammation, Fatigue
- Being tested
- Riluzole, Placebo
- Keywords
- Central Nervous System (CNS) Glutamate, Breast Cancer Treatment, Fatigue, Cognitive Dysfunction, Behavioral, Psychometrics, Imaging Technology, Magnetic Resonance Spectroscopy
- Medical subject headings
- Inflammation, Fatigue, Cognitive Dysfunction, Behavior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RiluzoleDrug
Also called Rilutek
Study participants randomized to this arm will take 100 mg/day of riluzole for 8 weeks.
PlaceboDrug
Study participants randomized to this arm will take a placebo, that matches the appearance of 100 mg tablets of riluzole, daily for 8 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Riluzole Arm | Experimental | 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). Receives: Drug: Riluzole |
| Placebo Arm | Placebo comparator | 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). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Central Nervous System (CNS) Glutamate Measured by Magnetic Resonance Spectroscopy (MRS)
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.
Measured: Baseline, Week 1, Week 8
Secondary outcomes (2)
Multidimensional Fatigue Inventory (MFI) Score
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.
Measured: Baseline, Weeks 1, 2, 4, 8
Patient-Reported Outcomes Measurement Information System (PROMIS) - Fatigue Short Form Score
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.
Measured: Baseline, Weeks 1, 2, 4, 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2016 (estimated)
- Study startApr 2016
- Primary completion24 Oct 2019
- Study completion24 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for InflammationStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Andrew H Miller, Emory University
- Investigators
- Andrew H Miller, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02796755
- Sponsor's protocol ID
- IRB00086271
- Status last verified
- Mar 2021
- First submitted
- 2 Jun 2016
- Last updated
- 14 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Riluzole on CNS Glutamate and Fatigue in Breast Cancer Survivors With High Inflammation
- ClinicalTrials.gov ID
- NCT02796755
- Acronym / sponsor ID
- IRB00086271
- Conditions
- Inflammation, Fatigue
- Keywords
- Central Nervous System (CNS) Glutamate, Breast Cancer Treatment, Fatigue, Cognitive Dysfunction, Behavioral, Psychometrics, Imaging Technology, Magnetic Resonance Spectroscopy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Study start
- Apr 2016
- Primary completion
- 24 Oct 2019 (actual)
- Study completion
- 24 Oct 2019 (actual)
- First posted
- 13 Jun 2016 (estimated)
- Results
- Posted 14 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Riluzole Arm | Experimental | Drug: RiluzoleParticipants 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). |
| Placebo Arm | Placebo comparator | Drug: PlaceboParticipants 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). |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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 1-5 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RiluzoleAlso: RilutekStudy participants randomized to this arm will take 100 mg/day of riluzole for 8 weeks. | Drug | Riluzole Arm |
| PlaceboStudy participants randomized to this arm will take a placebo, that matches the appearance of 100 mg tablets of riluzole, daily for 8 weeks. | Drug | Placebo Arm |
Primary outcome
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.
2 secondary outcomes
Multidimensional Fatigue Inventory (MFI) Score
Time frame: Baseline, Weeks 1, 2, 4, 8
Patient-Reported Outcomes Measurement Information System (PROMIS) - Fatigue Short Form Score
Time frame: Baseline, Weeks 1, 2, 4, 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew H Miller, MD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Riluzole in people with Inflammation and Fatigue, run by Emory University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Central Nervous System (CNS) Glutamate Measured by Magnetic Resonance Spectroscopy (MRS) (time frame: Baseline, Week 1, Week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2021.