Effects of Riluzole on CNS Glutamate and Fatigue in Breast Cancer Survivors With High Inflammation

NCT02796755 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: IRB00086271
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Inflammation; Fatigue

Keywords

Central Nervous System (CNS) Glutamate; Breast Cancer Treatment; Fatigue; Cognitive Dysfunction; Behavioral; Psychometrics; Imaging Technology; Magnetic Resonance Spectroscopy

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline, Week 1, Week 8

Secondary Outcomes (2)

• Multidimensional Fatigue Inventory (MFI) Score

  Baseline, Weeks 1, 2, 4, 8

• Patient-Reported Outcomes Measurement Information System (PROMIS) - Fatigue Short Form Score

  Baseline, Weeks 1, 2, 4, 8

Study Arms (2)

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).

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).

Drug: Placebo

Interventions

Riluzole DRUG

Study participants randomized to this arm will take 100 mg/day of riluzole for 8 weeks.

Also known as: Rilutek

Riluzole Arm

Placebo DRUG

Study participants randomized to this arm will take a placebo, that matches the appearance of 100 mg tablets of riluzole, daily for 8 weeks.

Placebo Arm

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead

Study Sites (1)

Emory University Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Inflammation; Fatigue; Cognitive Dysfunction; Behavior

Interventions

Riluzole

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Benzothiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Andrew H Miller, MD
• Organization: Emory University

amill02@emory.edu

404-727-8260

Study Officials

• Andrew H Miller, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 2, 2016
• First Posted: June 13, 2016
• Study Start: April 1, 2016
• Primary Completion: October 24, 2019
• Study Completion: October 24, 2019
• Last Updated: April 14, 2021
• Results First Posted: April 14, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)