Effects of Methylphenidate Versus Sustained Release Methylphenidate on Cognitive Functioning

Assessing the Efficacy of Immediate Release Methylphenidate, Sustained Release Methylphenidate and Modafinil for Patients With Brain Tumors

Primary Objective:

• To assess the efficacy of immediate release methylphenidate, sustained release methylphenidate, and the novel vigilance enhancing drug modafinil for the improvement of cognitive functioning in patients with brain tumors.

Study Overview

• Status: Terminated
• Conditions: Brain Tumor
• Intervention / Treatment: Drug: IR Methylphenidate; Drug: SR Methylphenidate; Drug: Modafinil

Detailed Description

All three drugs used in this clinical research study are widely used stimulants to help cancer patients who have fatigue and problems with concentration.

Before treatment starts, you will have a physical exam, including measurement of blood pressure, and neuropsychological and symptom evaluations. The neuropsychological evaluation is made up of tests of attention, memory, speech, and other brain functions, and takes about 30 minutes to complete. The other test evaluates symptoms you may be experiencing, such as fatigue or depression, and takes about 10 minutes to complete.

You will be randomly assigned (as in the toss of a coin) to one of three treatment groups. Participants in the first group will receive Immediate Release (IR) methylphenidate. Participants in the second group will receive Sustained Release (SR) methylphenidate. Participants in the third group will receive modafinil. There is an equal chance of being assigned to any of the groups. After you are randomized, you will contact the M. D. Anderson pharmacy to receive your assigned medication. You will receive a total of 5 weeks worth of medication. The extra week of medication is to allow for buffer should there be any conflict in rescheduling the follow-up evaluation.

IR methylphenidate is a pill taken twice a day. Both SR methylphenidate and modafinil are pills taken once a day. The amount of the medicine is the same for all three groups. You will take the medication every day for a total of 4 weeks.

You will be asked to complete a study calendar, which will be provided by the research staff. In the study calendar, you will be asked to initial after you take the study drug each day, and to record any side effects you may experience. You will be required to return the completed study calendar at the final evaluation visit, along with the empty bottles and any of the study drugs that may be left over.

You will remain on treatment for 4 weeks and return for a final evaluation. A follow-up neuropsychological evaluation and evaluation of symptoms will be performed. At the end of the study treatment period, you will be allowed to remain on active treatment if you wish to. You can discuss with your doctor whether to continue on the same medication or to try another one.

This is an investigational study. All of the study drugs are FDA approved and currently are used to help brain tumor patients. A total of 75 patients will take part in this study. All will be enrolled at M. D. Anderson.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • U.T.M.D. Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient diagnosed with a brain tumor, either primary or metastatic
2. Patient had prior radiation treatment to the brain
3. Patient is > or = 18 years of age
4. Patient has a Karnofsky performance status (KPS) performance of 70 at baseline
5. Patient is using acceptable birth control methods. Female participants (if of child bearing age and sexually active) and male participants (if sexually active with a partner of child-bearing potential) must use medically acceptable methods of birth control, including abstinence, birth control pills, diaphragm with spermicide, condom with foam or spermicide, vaginal spermicidal suppository or surgical sterilization.
6. Patient must speak and understand English or Spanish
7. Patient has reported cognitive decline and is being considered for stimulant therapy by their neurologist
8. Patient has provided written informed consent to participate in the study prior to enrollment to the study

Exclusion Criteria:

1. History of hypersensitivity reaction to methylphenidate or modafinil
2. History of severe headaches, glaucoma, major psychiatric diagnosis, narcolepsy, Tourette's syndrome, marked anxiety, tension or agitation
3. History of clinically significant pulmonary or cardiac disease
4. Uncontrolled hypertension: has not been on a stable treatment dose for the past month, or has a systolic pressure consistently greater than 140 mm Hg or diastolic pressure consistently greater than 90 mm Hg
5. Patients with uncontrolled seizures will be excluded
6. Current use of illicit drugs or history of alcohol or drug abuse and/or abuse potential
7. Moderate to severe depression (> 20 on Beck Depression Inventory II)
8. If taking antidepressants, patient must be on a stable dose
9. Currently taking psychostimulants, Monoamine oxidase (MAO) inhibitors, or anticoagulants
10. Current use of the following herbals or supplements for fatigue relief (dehydroepiandrosterone (DHEA), S-Adenosyl methionine (SAME), ginkgo, ginseng, St. John's Wort)
11. Any coexisting medical condition or are taking any concomitant medication that is likely to interfere with the safe administration of methylphenidate. Any potential interactions or coexisting medical condition not specified by the protocol will be determined by the prescribing physician as being exclusionary or not.
12. Patients currently taking any erythropoietin type drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Immediate Release (IR) Methylphenidate; 10 mg by mouth (PO) twice daily for 4 Weeks	Drug: IR Methylphenidate; 10 mg by mouth (PO) twice daily x 4 Weeks; Other Names: Ritalin
Active Comparator: Sustained Release (SR) Methylphenidate; 200 mg PO once daily for 4 Weeks	Drug: SR Methylphenidate; 18 mg PO Once Daily x 4 Weeks; Other Names: Ritalin
Active Comparator: Modafinil; 18 mg PO once daily for 4 Weeks	Drug: Modafinil; 200 mg PO Once Daily x 4 Weeks; Other Names: Provigil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Processing Speed Change From Baseline in the Trail-making Test Part A Score	'Trail Making Test Part A' is a neuropsychological test of visual attention and task switching, administered to measure processing speed, timed as participants follow "trail" made by consecutive numbers (1,2,3, etc.). The test is finished as quickly as possible, and the time taken to complete the test used as the primary performance metric (in seconds). Maximum time allowed is 300 seconds. A lower change score indicates improvement. Participants tested before starting study medication and 4-5 weeks later while on study medication, reflected in a z score (deviations from population mean).	Baseline to 4-5 weeks on study medication
Patient Cognitive Test Scores at End of Treatment Period	For cognitive assessment, set of widely used standardized psychometric instruments shown to be sensitive to neurotoxic effects of cancer treatment. Measures assess attention span (Digit Span), graphomotor speed (Digit Symbol), memory (Hopkins Verbal Memory Test-Revised), verbal fluency (Controlled Oral Words Association), visual motor scanning speed (Trail Making Test Part A), executive function (Trail Making Test Part B); motor speed and dexterity (Grooved Pegboard).	Baseline to end of Week 4 treatment period

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Investigators: Principal Investigator: Jeffrey S. Wefel, PhD, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• UT MD Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start: February 1, 2004
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: January 3, 2007
• First Submitted That Met QC Criteria: January 4, 2007
• First Posted (Estimate): January 5, 2007

Study Record Updates

• Last Update Posted (Actual): September 23, 2020
• Last Update Submitted That Met QC Criteria: September 1, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Brain Tumor; Fatigue; Concentration; Methylphenidate; Ritalin; Modafinil; Provigil
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Neoplasms; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Wakefulness-Promoting Agents; Methylphenidate; Modafinil
• Other Study ID Numbers: 2003-0925

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No