Drug Binding to DAT ReceptorsPhase 1/2NCT00593138
Study of Dopamine Transporter Receptor Occupancy With Long-acting Dex-methylphenidate
A Phase 1/2 study testing dex-methylphenidate in people with Drug Binding to DAT Receptors, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
The objectives of this study are to document the pharmacokinetics of the adequacy of DAT receptor occupancy d-MPH formulation in three doses (20 mg, 30 mg, and 40 mg) using PET scanning with C-11 Altropane as the ligand across a range of times. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Drug Binding to DAT Receptors
- What is being tested?
- dex-methylphenidate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2006to Dec 2009
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Signed written informed consent to participate in the study.
- Age: 18 -45, inclusive
- If female, non-pregnant, non-nursing with a negative serum pregnancy test.
- Female subjects will agree to use an acceptable and effective form of birth control during the course of their study participation.
- Supine and standing blood pressure < 150/90 mmHg.
- Heart rate, after resting for 5 minutes, within the range 46-90 beats/min.
- Right handed.
Who cannot join
- 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.
- Scores of Baseline Scales:
- Hamilton Depression Scale > 12 (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]
- Subjects with motor tics or with a family history or diagnosis of Tourette's Syndrome.
Show all 22Show fewer
- History of head trauma with loss of consciousness, organic brain disorders, seizures, or neurosurgical intervention.
- Any clinically significant chronic medical condition, in the judgment of the investigator.
- In the judgment of the investigator, has a mental impairment as evidenced by an I.Q. <75.
- Exposure to dopamine receptor antagonists within the previous three (3) months.
- Exposure to radiopharmaceuticals within four (4) weeks prior to PET scan.
- Subjects receiving psychotropic medication including MAO inhibitors within the past 6 to 12 months.
- Any clinically significant abnormality in the screening laboratory tests, vital signs, or 12 lead ECG, outside of normal limits.
- Any pre-existing structural cardiac abnormalities.
- A history or known family history of long QT syndrome or QTc >450 ms (males) or >470 ms (females).
- Any family history of cardiac sudden death.
- QTc prolongation of QTc > 450 ms (male) or 470 ms (female), hypertension or cardiac arrhythmia, or increased heart rate for age in the judgment of the investigator at screening.
- A history of cardiac structural abnormality
- Any woman of childbearing potential who is seeking to become pregnant or suspects that she may be pregnant.
- Subjects with a known recent history (within the past six (6) months) of illicit drug or alcohol dependence.
- Subjects diagnosed with glaucoma.
- Subjects at risk for MPH toxicity (e.g. individuals with arrhythmias, coronary artery disease, etc.).
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: A Randomized Open-label Study of Dopamine Transporter Receptor Occupancy With Long-acting Dex-methylphenidate (20 mg, 30 mg, and 40 mg) as Measured With C-11 Altropane in Healthy Adult Volunteers
The objectives of this study are to document the pharmacokinetics of the adequacy of DAT receptor occupancy d-MPH formulation in three doses (20 mg, 30 mg, and 40 mg) using PET scanning with C-11 Altropane as the ligand across a range of times. It has been estimated that MPH is effective when the average CNS DAT occupancy is 50% or greater. Focalin XR has been shown to be clinically effective in an analog classroom as early as 1 hour and as late as 12 hours. Therefore, it is hypothesized that the average DAT occupancy will be adequate (50% or greater) at time periods corresponding to the times of clinical efficacy.
The first objective is to examine the onset of action by testing whether average DAT occupancy will be adequate (50% or greater) at 1 hour after dosing for each dose tested (20 mg, 30 mg, 40 mg).
Read more
The second objective is to test the adequacy of average DAT occupancy in a range of later times for each dose. The times chosen (8, 10 and 12 hours) correspond to times Focalin XR has been shown to be clinically effective in an analogue classroom study. A range of times have been chosen since, while effective at 12 hours, the degree of clinical effectiveness decreased with later time periods. The adequacy of DAT occupancy across this range of time periods will provide important details on the in vivo molecular action of the medicine at periods of critical clinical activity.
The third exploratory objective is to examine a time period later then those previously tested with the highest dose. Since the clinical effectiveness of Focalin XR has not been tested out to 14 hours, it is unknown whether it is effective at 14 hours. If Focalin XR were to be effective at 14 hours it would be more likely at the highest dose.
Read the detailed description
Stimulants have been shown to be very effective in the treatment of Attention Deficit Hyperactivity Disorder (ADHD). [1] Studies have shown that full day treatment is often preferable to shorter treatment [2] and recent guidelines advise full day treatment. [3] However, there are many barriers to giving multiple doses of short acting medicine. New delivery systems have evolved to overcome tachyphylaxis and provide effective long-acting treatment with a single pill. [4] One of the new formulations is the spheroidal oral drug absorption system (SODAS). SODAS consists of capsules with two types of beads in a 1 to 1 ratio. One type of bead provides immediate release methylphenidate (IR MPH), and the other type of bead consists of MPH coated with a polymer that delays release for 4 hours. SODAS MPH has been shown to be effective in clinical studies [5]. However, the mechanism of action remains unclear. While pharmacokinetic studies have shown a double pulse profile in the serum [4], the central nervous system pharmacokinetics are unknown. Understanding the central nervous system pharmacokinetic properties is critical for new drug development for ADHD, especially for drugs of different lengths of action.
The d-MPH form has been shown to be the active enantiomer of MPH. Studies have shown that the duration of action of d-MPH is longer than that of racemic MPH. Clinical studies of once a day d-MPH has demonstrated efficacy in children, adolescents and adults with ADHD. Understanding the central nervous system pharmacokinetic properties of the SODAS formulation of the longer-acting (d) enantiomer will provide critical knowledge of its mechanism of action.
The main target of MPH in the brain is the dopamine transporter (DAT) [6]. There is now an exquisitely sensitive methodology to measure DAT occupancy using C-11 Altropane and Positron Emission Tomography (PET) [7]. The time course of decay of the C-11 Altropane permits repeated imaging, thus allowing documentation of the pharmacokinetics of DAT receptor occupancy. A group at Massachusetts General Hospital has previously documented the central nervous system pharmacokinetics of several psychiatric drugs using similar techniques [8-12].
To this end, this protocol seeks to document the pharmacokinetics of DAT receptor occupancy of d-MPH using PET and C-11 Altropane. It has been estimated that MPH is effective when the CNS DAT occupancy is 50% or greater. This aim of this study will be to measure CNS DAT occupancies at extended time points after administration of d-MPH. 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.
- Conditions
- Drug Binding to DAT Receptors
- Being tested
- dex-methylphenidate
- Keywords
- Focalin XR, Adult, PET scan
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dex-methylphenidateDrug
Also called Focalin XR
The drug is administered as a capsule by mouth. Participants are assigned to receive either 20, 30 or 40 mg doses before each scan visit.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: dex-methylphenidate |
What is being measured
The primary outcome is the main question the study is designed to answer.
DAT occupancy from PET scan results
Measured: each study visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2008 (estimated)
- Study startDec 2006
- Primary completionDec 2007
- Study completionDec 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Drug Binding to DAT ReceptorsStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Thomas J. Spencer, MD, Massachusetts General Hospital
- Investigators
- Thomas Spencer, MD, Principal investigator, MGH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00593138
- Sponsor's protocol ID
- 2006-p-001610
- Status last verified
- Oct 2013
- First submitted
- 28 Dec 2007
- Last updated
- 22 Oct 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Spencer TJ, Bonab AA, Dougherty DD, Mirto T, Martin J, Clarke A, Fischman AJ. Understanding the central pharmacokinetics of spheroidal oral drug absorption system (SODAS) dexmethylphenidate: a positron emission tomography study of dopamine transporter receptor occupancy measured with C-11 altropane. J Clin Psychiatry. 2012 Mar;73(3):346-52. doi: 10.4088/JCP.10m06393. Epub 2011 Nov 1.
PubMed 22154896
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Open-label Study of Dopamine Transporter Receptor Occupancy With Long-acting Dex-methylphenidate (20 mg, 30 mg, and 40 mg) as Measured With C-11 Altropane in Healthy Adult Volunteers
- ClinicalTrials.gov ID
- NCT00593138
- Acronym / sponsor ID
- 2006-p-001610
- Conditions
- Drug Binding to DAT Receptors
- Keywords
- Focalin XR, Adult, PET scan
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- Dec 2006
- Primary completion
- Dec 2007 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 14 Jan 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objectives of this study are to document the pharmacokinetics of the adequacy of DAT receptor occupancy d-MPH formulation in three doses (20 mg, 30 mg, and 40 mg) using PET scanning with C-11 Altropane as the ligand across a range of times. It has been estimated that MPH is effective when the average CNS DAT occupancy is 50% or greater. Focalin XR has been shown to be clinically effective in an analog classroom as early as 1 hour and as late as 12 hours. Therefore, it is hypothesized that the average DAT occupancy will be adequate (50% or greater) at time periods corresponding to the times of clinical efficacy.
The first objective is to examine the onset of action by testing whether average DAT occupancy will be adequate (50% or greater) at 1 hour after dosing for each dose tested (20 mg, 30 mg, 40 mg).
The second objective is to test the adequacy of average DAT occupancy in a range of later times for each dose. The times chosen (8, 10 and 12 hours) correspond to times Focalin XR has been shown to be clinically effective in an analogue classroom study. A range of times have been chosen since, while effective at 12 hours, the degree of clinical effectiveness decreased with later time periods. The adequacy of DAT occupancy across this range of time periods will provide important details on the in vivo molecular action of the medicine at periods of critical clinical activity.
The third exploratory objective is to examine a time period later then those previously tested with the highest dose. Since the clinical effectiveness of Focalin XR has not been tested out to 14 hours, it is unknown whether it is effective at 14 hours. If Focalin XR were to be effective at 14 hours it would be more likely at the highest dose.
Detailed description
Stimulants have been shown to be very effective in the treatment of Attention Deficit Hyperactivity Disorder (ADHD). [1] Studies have shown that full day treatment is often preferable to shorter treatment [2] and recent guidelines advise full day treatment. [3] However, there are many barriers to giving multiple doses of short acting medicine. New delivery systems have evolved to overcome tachyphylaxis and provide effective long-acting treatment with a single pill. [4] One of the new formulations is the spheroidal oral drug absorption system (SODAS). SODAS consists of capsules with two types of beads in a 1 to 1 ratio. One type of bead provides immediate release methylphenidate (IR MPH), and the other type of bead consists of MPH coated with a polymer that delays release for 4 hours. SODAS MPH has been shown to be effective in clinical studies [5]. However, the mechanism of action remains unclear. While pharmacokinetic studies have shown a double pulse profile in the serum [4], the central nervous system pharmacokinetics are unknown. Understanding the central nervous system pharmacokinetic properties is critical for new drug development for ADHD, especially for drugs of different lengths of action.
The d-MPH form has been shown to be the active enantiomer of MPH. Studies have shown that the duration of action of d-MPH is longer than that of racemic MPH. Clinical studies of once a day d-MPH has demonstrated efficacy in children, adolescents and adults with ADHD. Understanding the central nervous system pharmacokinetic properties of the SODAS formulation of the longer-acting (d) enantiomer will provide critical knowledge of its mechanism of action.
The main target of MPH in the brain is the dopamine transporter (DAT) [6]. There is now an exquisitely sensitive methodology to measure DAT occupancy using C-11 Altropane and Positron Emission Tomography (PET) [7]. The time course of decay of the C-11 Altropane permits repeated imaging, thus allowing documentation of the pharmacokinetics of DAT receptor occupancy. A group at Massachusetts General Hospital has previously documented the central nervous system pharmacokinetics of several psychiatric drugs using similar techniques [8-12].
To this end, this protocol seeks to document the pharmacokinetics of DAT receptor occupancy of d-MPH using PET and C-11 Altropane. It has been estimated that MPH is effective when the CNS DAT occupancy is 50% or greater. This aim of this study will be to measure CNS DAT occupancies at extended time points after administration of d-MPH. 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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: dex-methylphenidate |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Signed written informed consent to participate in the study.
- Age: 18 -45, inclusive
- If female, non-pregnant, non-nursing with a negative serum pregnancy test.
- Female subjects will agree to use an acceptable and effective form of birth control during the course of their study participation.
- Supine and standing blood pressure < 150/90 mmHg.
Key exclusion criteria (22 listed)
- 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.
- Scores of Baseline Scales:
- Subjects with motor tics or with a family history or diagnosis of Tourette's Syndrome.
- History of head trauma with loss of consciousness, organic brain disorders, seizures, or neurosurgical intervention.
- Any clinically significant chronic medical condition, in the judgment of the investigator.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| dex-methylphenidateAlso: Focalin XRThe drug is administered as a capsule by mouth. Participants are assigned to receive either 20, 30 or 40 mg doses before each scan visit. | Drug | 1 |
Primary outcome
DAT occupancy from PET scan results
Time frame: each study visit
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2013.
- Derived from this study: PubMed 22154896Spencer TJ, Bonab AA, Dougherty DD, Mirto T, Martin J, Clarke A, Fischman AJ. Understanding the central pharmacokinetics of spheroidal oral drug absorption system (SODAS) dexmethylphenidate: a positron emission tomography study of dopamine transporter receptor occupancy measured with C-11 altropane. J Clin Psychiatry. 2012 Mar;73(3):346-52. doi: 10.4088/JCP.10m06393. Epub 2011 Nov 1.
- Related InfoLink provided by the sponsor.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas Spencer, MD principal investigator
MGH
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing dex-methylphenidate in people with Drug Binding to DAT Receptors, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Oct 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DAT occupancy from PET scan results (time frame: each study visit). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00593138, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2013.