Trial Information

Effects of Low-Dose Naltrexone on Quality of Life in High-Grade Glioma Patients: A Placebo-Controlled, Double-Blind Randomized Trial

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 pre-determined 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 LDN dosed at 4.5 mg orally to be taken every evening before going to bed.
Patients will be assessed at the following timepoints: 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). (See
Figure 1 for study design) 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 discontinued 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 cc
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 Survery (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.