Low Dose Naltrexone for Glioma Patients

• ClinicalTrials.gov Identifier: NCT01303835
• Recruitment Status: Completed
• First Posted: February 25, 2011
• Results First Posted: June 26, 2015
• Last Update Posted: July 17, 2015
• Sponsor: Katy Peters
• Information provided by (Responsible Party): Katy Peters, Duke University

Tracking Information

• First Submitted Date: February 23, 2011
• First Posted Date: February 25, 2011
• Results First Submitted Date: May 8, 2015
• Results First Posted Date: June 26, 2015
• Last Update Posted Date: July 17, 2015
• Study Start Date: May 2011
• Actual Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 4, 2015)

Effects of Low-dose Naltrexone Versus Placebo on Change in Quality of Life (QoL) in High-grade Glioma Patients Undergoing Standard Chemoradiation From Baseline [ Time Frame: Baseline and 16 weeks ]

The difference in QoL scores between the 3rd QoL measurement (approximately 16 weeks from initial assessment) and the initial baseline assessment are reported. QoL instruments included are listed below. Higher scores indicate more favorable outcomes unless otherwise indicated.

• Functional Assessment of Cancer Therapy-Brain (FACT-Br) measures general QoL reflecting symptoms associated with brain malignancies (range 0-132)
• Functional Assessment of Chronic Illness Therapy (FACIT-F) measures level of fatigue during patients' usual daily activities (range 0-52)
• Epworth Sleepiness Scale measures level of daytime sleepiness. Note that higher scores indicate a greater level of sleepiness (range 0-24)
• Medical Outcomes Survey (MOS) measures QoL including physical, mental and general health via 8 domains (range 0-100 for each domain)
• Zung Self-Rating Depression Scale quantifies the depressed status of a patient. Lower scores indicate more favorable outcome (range 20-80) A difference

Original Primary Outcome Measures (submitted: February 23, 2011)

Effects of low-dose naltrexone versus placebo on quality of life in high-grade glioma patients undergoing standard chemoradiation. [ Time Frame: 24 weeks ]

Patient-Reported Outcomes as assessed by standardized and validated questionnaires including: Quality of Life; Fatigue; Cognition; Depression; Computerized Battery from CNS Vital Signs (Medical Outcomes Survey, Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Zung Self-Rating Depression Scale)

Current Secondary Outcome Measures (submitted: June 4, 2015)

• Effects of Low-dose Naltrexone Versus Placebo on Change in Functional Capacity From Baseline [ Time Frame: Baseline and 16 weeks ]
  Patients completed the 6-minute walk test (6MWT) at each QoL measurement assessment. The 6 minute walk test is a measure of functional capacity in which the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes is measured. The mean difference in distance traveled (in meters) between the 3rd QoL measurement (approximately 16 weeks from initial assessment) and the initial baseline assessment are reported. A difference greater than 0 indicates an increase in distance traveled, while a difference less than 0 indicates a decrease.
• Effects of Low-dose Naltrexone Versus Placebo on Change in Neurocognitive Function From Baseline [ Time Frame: Baseline and 16 weeks ]
  Patients completed neurocognitive testing at each QoL measurement assessment. Neurocognitive function was measured via a computerized neurocognitive test battery called CNS Vital Signs. The battery consists of 7 tests that assess verbal and visual memory, finger tapping, symbol digit coding, the Stroop Test, a test of shifting attention, and continuous performance. The battery provides scores over 9 domains with higher scores indicating better performance. Scores were normalized to a standard score mean of 100 and standard deviation of 15 using a normative sample. The mean difference in score in each domain between the 3rd QoL measurement (approximately 16 weeks from initial assessment) and the initial baseline assessment are reported. A difference greater than 0 indicates an increase in mean score, while a difference less than 0 indicates a decrease in mean score.

Original Secondary Outcome Measures (submitted: February 23, 2011)

Compare the effects of low-dose naltrexone versus placebo on functional capacity and compare the effects on neurocognition in high-grade glioma patients [ Time Frame: 24 weeks ]

• Functional Capacity (Six-minute walk test)
• Neurocognitive Function (a computerized neurocognitive test battery called CNS Vital Signs® including verbal memory test, visual memory test, finger tapping test, symbol digit coding, Stroop test, shifting attention test, continuous performance test)
• Adverse Event Monitoring
• Laboratory Testing

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Low Dose Naltrexone for Glioma Patients
• Official Title: Effects of Low Dose Naltrexone on Quality of Life in High Grade Glioma Patients: A Placebo-Controlled, Double-Blind Randomized Trial
• Brief Summary: To compare the effects of low dose naltrexone (LDN) versus placebo on quality of life in high grade glioma patients undergoing standard chemoradiation

Detailed Description

The proposed study is a placebo-controlled, randomized clinical trial. Potential participants will be identified via clinical protocol chart review of patients scheduled to attend their predetermined follow-up consultations at The Preston Robert Tisch Brain Tumor Center (PRT-BTC) at Duke University Medical Center after evaluation of treatment for newly diagnosed high grade gliomas. We will identify high grade glioma patients that will receive standard chemoradiation (radiotherapy with daily temozolomide dosed at 75 mg/m2). After obtaining written informed consent, all participants will be scheduled for baseline study assessments before starting radiotherapy. Patients will be randomized to receive either placebo or low dose naltrexone (LDN) dosed at 4.5 mg orally to be taken every evening before going to bed. Patients will be assessed at the following time points: 1. Baseline (before chemoradiation), 2. After chemoradiation (approximately 8 weeks from initial assessment), 3. Two months after standard chemoradiation (approximately 16 weeks after initial assessment), and 4. Four months after standard chemoradiation (approximately 24 weeks after initial assessment). Treatment with LDN or placebo will begin on first day of chemoradiation and will be continued for a total of 16 weeks from initial assessment. Last assessment at 24 weeks will occur 8 weeks after discontinuation of LDN or placebo. All visits will be linked to patients' clinical management visits. All testing will be performed at PRT-BTC and at Duke University Medical Center.

The following procedures will be obtained at each assessment visit:

1. Complete a six-minute walk test. The exercise test is designed to determine how far the subject can walk in six minutes. This test will take place at the PRT-BTC at Duke University Medical Center with appropriate medical supervision.
2. Blood testing that will be performed as part of each clinic visit. Approximately 10 milliliters or 2 teaspoons of blood will be drawn at each visit. This will not be additional blood work, but rather the standardized blood work that the subject will need for evaluation associated with radiation and chemotherapy treatments.

We will ask the subject to complete the following tests/questionnaires:

1. Neurocognitive testing: this testing will be performed using a computer program called CNS Vital Signs®. This program consists of verbal and visual memory tests, attention tests, reasoning tests, and speed of processing tests. The subject will use a laptop computer to complete these tests. No previous exposure to computers or computer testing is needed to complete the test.
2. Computerized Questionnaires: Four questionnaires will be presented using a computerized program. These will include Medical Outcomes Survey (MOS), Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and Zung Self-Rating Depression Scale (ZSDS). MOS assesses general health, well-being, and quality of life. ESS asks about level of sleepiness while PSQI asks about sleep quality. Finally, ZSDS will evaluate feelings of depression and sadness.
3. Beck depression inventory (BDI): This questionnaire asks questions about the subject's levels of sadness, changes in the subject's mood, sleeping and eating patterns, the subject's level of interest in activities, thoughts and feelings the subject is having and the subject's level of concentration. This is a pen and paper questionnaire.
4. Functional Assessment of Cancer Therapy-Brain (FACT-BR) scale: This questionnaire asks questions about physical, function, emotional, and social well-being. This is a pen and paper questionnaire.
5. Functional Assessment of Cancer Therapy-Fatigue (FACIT-F) scale: This questionnaire asks questions about fatigue. This is a pen and paper questionnaire.
6. Functional Assessment of Cancer Therapy-Cognition (FACT-Cog) scale: This questionnaire asks questions about your thinking and ability to do memory, attention, and reasoning activities. This is a pen and paper questionnaire.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Malignant Glioma

Intervention

• Drug: LDN
  Randomized patients received 4.5 mg low dose naltrexone (LDN) to be taken every night before bed.
  Other Names:

  • Low dose naltrexone
  • ReVia
• Drug: Placebo
  Randomized patients received placebo to be taken every night before bed.

Study Arms

• Experimental: Naltrexone
  Randomized patients received 4.5 mg low dose naltrexone (LDN) to be taken every night before bed.
  Intervention: Drug: LDN
• Placebo Comparator: Placebo
  Randomized patients received placebo to be taken every night before bed.
  Intervention: Drug: Placebo

• Publications *: Peters KB, Affronti ML, Woodring S, Lipp E, Healy P, Herndon JE 2nd, Miller ES, Freeman MW, Randazzo DM, Desjardins A, Friedman HS. Effects of low-dose naltrexone on quality of life in high-grade glioma patients: a placebo-controlled, double-blind randomized trial. Support Care Cancer. 2022 Apr;30(4):3463-3471. doi: 10.1007/s00520-021-06738-0. Epub 2022 Jan 10.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 4, 2015): 110
• Original Estimated Enrollment (submitted: February 23, 2011): 72
• Actual Study Completion Date: May 2015
• Actual Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• written informed consent prior to beginning specific protocol procedures
• histologically proven high-grade glioma
• planned treatment with concurrent radiotherapy and daily oral temozolomide (with or without Avastin)
• ≥ 18 years of age
• Karnofsky performance index ≥ 70%
• must be able to ambulate unassisted for 6 minutes safely
• The Preston Robert Tisch Brain Tumor Center (PRT-BTC) neuro-oncologist's approval
• hematocrit ≥ 29%, hemoglobin ≥ 9, absolute neutrophil count (ANC) ≥ 1,500 cells/microliter, platelets ≥ 100,000 cells/microliter
• serum creatinine < 1.5 times upper limit of normal, serum glutamic oxaloacetic transaminase (SGOT) < 2.5 times upper limit of normal and bilirubin < 2.0 times upper limit of normal
• if sexually active, patients will take contraceptive measures for the duration of the treatments
• Women of childbearing potential must have a negative serum pregnancy test within 48 hours prior to administration of study drug

Exclusion Criteria:

• prior therapy with naltrexone or naloxone
• co-medication that may interfere with study results, e.g. opioids,
• known hypersensitivity to any component of naltrexone
• pregnant (positive pregnancy test) or lactating

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01303835
• Other Study ID Numbers: Pro00027661
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Katy Peters, Duke University
• Original Responsible Party: Katherine Peters, MD, PhD, Duke University Medical Center
• Current Study Sponsor: Katy Peters
• Original Study Sponsor: Duke University
• Collaborators: Not Provided

Investigators

• Principal Investigator: Katherine B Peters, MD, PhD; Duke University

• PRS Account: Duke University
• Verification Date: June 2015