This study is an attempt to seriously investigate one of the most plausible reasons for the difference in effectiveness of MPH in the treatment of adult ADHD patients with and without SUD.
ID
Source
Brief title
Condition
- Other condition
- Psychiatric disorders
Synonym
Health condition
verslaving
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Does baseline DAT binding differ in ADHD+SUD and ADHD-SUD patients?
Does MPH affect DAT binding differently in ADHD+SUD and ADHD-SUD patients?
Secondary outcome
Does MPH differentially affect ADHD symptoms and ADHD associated cognitive
functions in ADHD patients with and without cocaine dependence?
Does DAT occupancy affect drug craving and drug use in ADHD+SUD patients?
Background summary
Attention deficit hyperactivity disorder (ADHD) may play a role in the etiology
and pathogenesis of substance use disorders (SUD) although its relationship to
substance abuse is not fully understood.
The dopamine transporter (DAT) plays a fundamental role in both ADHD and SUD.
DAT-selective medications, such as methylphenidate (MPH), have been shown to
successfully block the DAT in ADHD patients and DAT occupancy has been
associated with clinical effectiveness. In ADHD patients with SUD, however,
these medications are not very effective, neither for treating ADHD nor SUD.
Thus, ADHD patients with SUD are often not responsive to MPH. This raises two
important questions: why are patients with ADHD with SUD not responsive to
adequate doses of MPH and how does this relate to SUD?
It is hypothesized that adult ADHD patients with SUD generally have higher
baseline DAT availability in the basal ganglia, and that similar doses of MPH
result in lower occupancy rates in adult ADHD patients with SUD compared to
adult ADHD patients without SUD. It remains unclear whether baseline DAT
density and DAT occupancy following MPH treatment differs between ADHD patients
with and without SUD. These are relevant concerns since answers to these
questions may shed light on the lack of efficacy of MPH for the treatment of
ADHD symptoms and drug use in ADHD patients with comorbid SUD.
Study objective
This study is an attempt to seriously investigate one of the most plausible
reasons for the difference in effectiveness of MPH in the treatment of adult
ADHD patients with and without SUD.
Study design
Our hypotheses will be tested using [123I]FP-CIT single photon emission
computed tomography (SPECT) to assess DATs in-vivo in two groups of adult ADHD
patients, one with a comorbid diagnosis of cocaine dependence (ADHD+SUD, n=30)
and one without a comorbid substance use disorder (ADHD-SUD, n=30).
Intervention
We will use [123I]FP-CIT single photon emission computed tomography (SPECT) to
assess DATs in-vivo before and after MPH treatment
Study burden and risks
The burden for the participant consists of exposures to 2 SPECT scans,
questionaires and neuropsychological testing. Also, 4 blood samples (1 during
each SPECT scan, 1 for genetics, and 1 at the end of treatment to check for
study compliance and MPH plasma levels) and weekly urine tests will be obtained.
Participants will also ingest methylphenidate daily during 3 weeks.
The risks for the participants include: exposure to the radiotracer, and
possible side effects of methylphenidate (see protocol pg 8).
Meibergdreef 9
1105 AZ Amsterdam
NL
Meibergdreef 9
1105 AZ Amsterdam
NL
Listed location countries
Age
Inclusion criteria
1. Male, age 18-60 years;
2. Current DSM-IV diagnosis of adult ADHD for all participants;
3. For the ADHD+cocaine dependent group: Current DSM-IV diagnosis of cocaine dependence, but abstinent from cocaine use for at least 1 week;
4. Able to provide written informed consent and to comply with all study procedures;
5. Negative urine analyses for methylphenidate, amphetamines and cocaine.
Exclusion criteria
1. Currently dependent on any substance other than cocaine or nicotine;
2. History of severe depression, i.e. depression necessitating hospitalization, a history of 2 or more recurrent episodes of depression or previous suicide attempts;
3. Severe neurological or psychiatric disorders or diseases (e.g., psychosis, bipolar depression, Parkinson*s disease, or dementia) that require psychotropic or ECG abnomedications;
4. Serious medical illnesses that would make participation hazardous, such as cardiovascular disease;
5. Known hypersensitivity or allergy to methylphenidate;
6. Under therapy with drug known to influence binding to DATs, including antipsychotics, MPH, bupropion, and dexamphetamine within 30 days prior to randomization;
7. Received a drug with known potential for toxicity to a major organ system within the month prior to entering treatment;
8. Clinically significant abnormal laboratory values (*3x normal) as measured by the treatment center;
9. Any disease of the gastrointestinal system, liver, or kidneys which could result in altered metabolism or excretion of the study medication;
10. Hypersensitivity to Iodine.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-012261-61-NL |
| CCMO | NL27983.018.09 |
| OMON | NL-OMON24052 |