Effects of Methylphenidate Versus Sustained Release Methylphenidate on Cognitive Functioning

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00418691
• Collaborator: (none)
• Enrollment: 34
• Location: 1
• Arms: 3
• Duration (Months): 69
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Brain Tumor	Drug: IR Methylphenidate; Drug: Modafinil; Drug: SR Methylphenidate	Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Assessing the Efficacy of Immediate Release Methylphenidate, Sustained Release Methylphenidate and Modafinil for Patients With Brain Tumors
• Study Start Date: Feb 1, 2004
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Nov 1, 2009

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Mean Processing Speed Change From Baseline in the Trail-making Test Part A Score [Baseline to 4-5 weeks on study medication]

   '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).

2. Patient Cognitive Test Scores at End of Treatment Period [Baseline to end of Week 4 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	U.T.M.D. Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• UT MD Anderson Cancer Center

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00418691
• Other Study ID Numbers: 2003-0925
• First Posted: Jan 5, 2007
• Last Update Posted: Sep 23, 2020
• Last Verified: Sep 1, 2020

• Keywords provided by M.D. Anderson Cancer Center: Brain Tumor; Methylphenidate; Ritalin; Modafinil; Provigil; Fatigue; Concentration
• Additional relevant MeSH terms: Brain Neoplasms; Methylphenidate; Modafinil

Study Results

Participant Flow

Recruitment Details	Recruitment Period: March 2004 - April 2009. All recruiting done at UT MD Anderson Cancer Center, Neuro-Oncology Clinic.
Pre-assignment Detail	Of the 34 registered patients, one enrolled patient did not join study and therefore was never included in any group assignment.

Arm/Group Title	IR Methylphenidate	SR Methylphenidate	Modafinil
Arm/Group Description	Immediate Release (IR) Methylphenidate 10 mg by mouth (PO) twice daily for 4 weeks	Sustained Release (SR) Methylphenidate 200 mg PO once daily for 4 weeks	18 mg PO once daily for 4 weeks
Period Title: Overall Study
STARTED	11	12	10
COMPLETED	9	10	5
NOT COMPLETED	2	2	5

Baseline Characteristics

Arm/Group Title	IR Methylphenidate	SR Methylphenidate	Modafinil	Total
Arm/Group Description	Immediate Release (IR) Methylphenidate 10 mg by mouth (PO) twice daily for 4 weeks	Sustained Release (SR) Methylphenidate 200 mg PO once daily for 4 weeks	18 mg PO once daily for 4 weeks	Total of all reporting groups
Overall Participants	11	12	10	33
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	11 100%	12 100%	7 70%	30 90.9%
>=65 years	0 0%	0 0%	3 30%	3 9.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.9 (10.0)	41.2 (10.5)	53.8 (12.9)	46.6 (12.0)
Sex: Female, Male (Count of Participants)
Female	6 54.5%	6 50%	4 40%	16 48.5%
Male	5 45.5%	6 50%	6 60%	17 51.5%
Region of Enrollment (participants) [Number]
United States	11 100%	12 100%	10 100%	33 100%

Outcome Measures

1. Primary Outcome

Title	Mean Processing Speed Change From Baseline in the Trail-making Test Part A Score
Description	'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).
Time Frame	Baseline to 4-5 weeks on study medication

Outcome Measure Data

Analysis Population Description

Analysis were per protocol. The z-score reflects how many standard deviations above or below the population mean a raw score is for each participant.

Arm/Group Title	IR Methylphenidate	SR Methylphenidate	Modafinil
Arm/Group Description	Immediate Release (IR) Methylphenidate 10 mg by mouth (PO) twice daily for 4 weeks	Sustained Release (SR) Methylphenidate 200 mg PO once daily for 4 weeks	18 mg PO once daily for 4 weeks
Measure Participants	11	12	10
Mean (Standard Deviation) [z-scores]	-4.7 (9.2)	0.24 (1.0)	-3.7 (4.1)

2. Primary Outcome

Title	Patient Cognitive Test Scores at End of Treatment Period
Description	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).
Time Frame	Baseline to end of Week 4 treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	2 years and 11 months
Arm/Group Title	IR Methylphenidate		SR Methylphenidate		Modafinil
Arm/Group Description	Immediate Release (IR) Methylphenidate 10 mg by mouth (PO) twice daily for 4 weeks		Sustained Release (SR) Methylphenidate 200 mg PO once daily for 4 weeks		18 mg PO once daily for 4 weeks
All Cause Mortality
	IR Methylphenidate		SR Methylphenidate		Modafinil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	IR Methylphenidate		SR Methylphenidate		Modafinil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/12 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	IR Methylphenidate		SR Methylphenidate		Modafinil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/12 (0%)		0/10 (0%)

Limitations/Caveats

Early termination lead to limited analysis.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.