Low Dose Naltrexone for Glioma Patients

Phase 2

Completed

Conditions: Malignant Glioma

Interventions: Drug: Placebo
Drug: LDN

Registration Number: NCT01303835

Lead Sponsor: Katy Peters

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 110

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Randomized patients received placebo to be taken every night before bed.
Naltrexone	LDN	Randomized patients received 4.5 mg low dose naltrexone (LDN) to be taken every night before bed.

Primary Outcome Measures

Name	Time	Method
Effects of Low-dose Naltrexone Versus Placebo on Change in Quality of Life (QoL) in High-grade Glioma Patients Undergoing Standard Chemoradiation From Baseline	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

Secondary Outcome Measures

Name	Time	Method
Effects of Low-dose Naltrexone Versus Placebo on Change in Functional Capacity From Baseline	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	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.