An Open Label Phase I/II Study of Dopamine Transporter Receptor Occupancy With OROS and Immediate Release Methylphenidate as Measured With C-11 Altropane in Human Subjects
Information source: Massachusetts General Hospital
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Healthy Volunteers
Intervention: OROS methylphenidate hydrochloride (Drug); immediate release methylphenidate hydrochloride (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: Massachusetts General Hospital Official(s) and/or principal investigator(s):
Thomas Spencer, MD, Principal Investigator, Affiliation: Massachusetts General Hospital
Summary
The specific aim of this study is to document the pharmacokinetics of DAT receptor occupancy
of OROS and immediate release (IR) MPH using PET scanning with C-11 altropane as the ligand.
We hypothesize that the time to maximal receptor occupancy and the degree of receptor
occupancy of immediate release (IR) MPH will be shorter and greater (respectively) than with
an equipotent dose of OROS MPH.
Clinical Details
Official title: An Open Label Phase I/II Study of Dopamine Transporter Receptor Occupancy With OROS and Immediate Release Methylphenidate as Measured With C-11 Altropane in Human Subjects
Study design: Randomized, Single Blind, Historical Control, Parallel Assignment
Primary outcome: The DAT receptor occupancy of OROS MPH and Metadate CD using PET scanning with C-11 Altropane. Objective measures also provided by d and l ritalinic acid and methylphenidate levels at pre-dose through hour 10.
Detailed description:
This protocol seeks to document the pharmacokinetics of DAT receptor occupancy of OROS and
immediate release (IR) MPH using PET and C-11 altropane. The main target of MPH in the brain
is the dopamine transporter (DAT). We have an exquisitely sensitive methodology to measure
DAT occupancy using C-11 Altropane and Positron Emission Tomography (PET). This research will
provide novel and unique information toward a better understanding of the mechanism of
action of long-acting stimulant formulations to enable new drug development and an estimation
of the relative abuse potential of the current formulation.
Eligibility
Minimum age: 18 Years.
Maximum age: 55 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Signed written informed consent to participate in the study.
2. Age: 18 – 55
3. If female, non-pregnant, non-nursing with a negative serum pregnancy test and using an
adequate form of birth control.
4. Supine and standing blood pressure within the range 110/60 to 150/90 mmHg.
5. Heart rate, after resting for 5 minutes, within the range 46-90 beats/min.
6. Subjects who are within 20% of the ideal weight for height as
7. Right handed.
Exclusion Criteria:
1. Diagnosis of any psychotic disorder, bipolar disorder, severe depression, severe
anxiety, or Autism. Subjects with mild mood, oppositional, conduct, and anxiety
disorders may be permitted to participate if considered appropriate by the
investigator.
2. Scores of Baseline Scales:
Hamilton Depression Scale > 17 (out of a possible 67 on the 21-item scale)[18] Beck
Depression Inventory > 19 (out of a possible 63 on the 21-item scale)[19] Hamilton
Anxiety Scale > 21 (out of a possible 56 on the 14-item scale) [20]
3. Tics or Tourette’s Syndrome.
4. History of head trauma with loss of consciousness, organic brain disorders, seizures,
or neurosurgical intervention.
5. Any clinically significant chronic medical condition, in the judgment of the
investigator.
6. Mental impairment as evidenced by an I. Q. <75.
7. Exposure to dopamine receptor antagonists within the previous three (3) months.
8. Exposure to radiopharmaceuticals within four (4) weeks prior to PET scan.
9. Subjects receiving psychotropic medication.
10. Any clinically significant abnormality in the screening laboratory tests, vital signs,
or 11-lead ECG, outside of normal limits.
12. Any woman of childbearing potential who is seeking to become pregnant or suspects that
she may be pregnant.
13. Subjects with a known recent history (within the past six (6) months) of illicit drug
or alcohol dependence
Locations and Contacts
Massachusetts General Hospital, Cambridge, Massachusetts 02138, United States
Additional Information
Starting date: January 2004
Ending date: April 2004
Last updated: March 10, 2006
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