View Clinical Trial (Medical Research Study)
Development of Induced Pluripotent Stem Cells Carrying Monoamine Transporter Polymorphisms
| City: |
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Baltimore |
| State: |
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Maryland |
| Zip Code: |
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21224 |
| Conditions: |
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Induced Pluripotent Stem Cells |
| Purpose: |
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Background:
- Researchers are interested in studying the roles that genes play in drug and alcohol
addiction. Genes seem to account for about half of the differences between people who become
addicted to drugs and people who do not. This study will collect blood and skin cell
samples. These cells will be used to develop stem cells that are useful for studying how
genes are related to drug use and dependence.
Objectives:
- To study genetic and cellular differences between people who are addicted to drugs and
those who are not.
Eligibility:
- Individuals between 21 and 65 years of age who do not use drugs.
- Individuals between 21 and 65 years of age who are in treatment with buprenorphine or
methadone.
Design:
- Participants will be screened with a brief physical exam and medical history.
- Participants will also answer questions about physical and mental health, quality of
life, and history of drug and alcohol use. A urine sample and cheek swab sample will be
collected.
- Participants whose genetic samples match the study requirements will be asked to come
back to provide a skin biopsy sample and a second urine sample.
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| Study Summary: |
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Background - The molecular- and cellular-based mechanisms that contribute to the initiation
and development of addiction remain to be elucidated. Estimates have suggested that 40-60
percent of the vulnerability to addiction may be attributable to genetic aberrations.
Multiple chromosomal regions have been linked to addiction including those containing the
dopamine transporter (DAT) and vesicular monoamine transporter (VMAT2) genes. Current
efforts to understand how polymorphisms in these monoamine transporters contribute to the
molecular mechanisms of addiction are severely hindered by the inability to directly
interrogate neural cell types from the patients. There is great potential for
patient-specific iPS cell technology to profoundly impact our understanding of human
development and disease by providing genetically distinct, functional sources of human
cells.
Objective - The objective of the research is to develop a cell-based system whereby neural
cells from afflicted individuals can be functionally assayed to interrogate the molecular
mechanisms underlying addiction.
Study population - Controls (non-drug users) and opioid dependent adults receiving opioid
agonist therapy aged 21- 65 will be enrolled.
Design - Participants' demographic characteristics, psychosocial evaluation, and
psychiatric, medical, and drug use histories will be characterized. DNA will be collected
via cheek swabs of up to 30 potential participants for determination of dopamine transporter
(DAT) and vesicular monoamine transporter (VMAT2) gene polymorphisms. Participants (N=16)
with suitable polymorphisms will be asked to under go skin biopsies; 2 individuals for each
of two genotypes for each gene (DAT or VMAT), i.e., 8 samples from addicts and 8 samples for
control subjects. Collaborators at Case Western Reserve University will use the skin cells
to derive and characterize patient-specific, induced pluripotent stem (iPS) cells that carry
monoamine transporter polymorphisms for the hDAT1 and hVMAT2 genes. They will differentiate
patient-specific iPS cells line into dopaminergic neurons and carry out a detailed and
functional characterization of these cells to identify their molecular characteristics.
Outcome measures - Biological specimens from the addiction patients and controls will be
used to derive and characterize patient-specific, induced pluripotent stem (iPS) cells that
carry monoamine transporter polymorphisms. Patient-specific iPS cells lines will be
differentiated into dopaminergic neurons. In follow up studies, we will characterize,
compare, and functionally assay these patient-specific, iPS cell-derived dopaminergic
neurons from control and addiction patients that carry polymorphisms for hDAT1 and hVMAT2
gene to investigate any possible association with dopamine neurotransmission variations and
vulnerability to addiction.
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| Criteria: |
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- INCLUSION CRITERIA:
1. 21 to 65 years old
Opioid dependent participant group only:
2. enrollment in a substance abuse treatment protocol in Archway.
Non-drug users
3. no lifetime history of drug dependence as indicated by the screening ASI and
Substance Abuse/Dependence Evaluation counselor interview.
EXCLUSION CRITERIA:
1. Relevant neurological disorders (including, but not limited to, Parkinson's disease
and Huntington's disease).
2. contraindications to skin biopsy including, but not limited to, bleeding disorders,
skin disorders, and immune disorders, that the MAI determines may alter the risk of
the biopsy.
3. cognitive impairment severe enough to preclude informed consent or valid responses on
questionnaires.
4. controls will also be excluded if they test positive for drugs or alcohol during
screening or study visits.
5. unwillingness to allow samples to be kept for future research.
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| NCT ID: |
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NCT01534624 |
| Primary Contact: |
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Principal Investigator
Kenzie Preston, Ph.D.
National Institute on Drug Abuse (NIDA)
Kenzie Preston, Ph.D.
Phone: (443) 740-2326
Email: kpreston@intra.nida.nih.gov
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| Backup Contact: |
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N/A |
| Location Contact: |
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Baltimore, Maryland 21224
United States
For more information contact Mathew's Media Group Recruiting
Phone: 800-535-8254
Email: researchstudies@mail.nih.gov
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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May 18, 2013 |
| Modifications to this listing: |
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