In vivo imaging and quantification of central norepinephrine transporters (NET) by [11C]MRB positron emission tomography (PET)/magnetic resonance imaging (MRI) in adult patients with attention-deficit/hyperactivity disorder (ADHD) and emotional dysregulation (ED)

Organizational Data

DRKS-ID:
DRKS00032396
Recruitment Status:
Recruiting planned
Date of registration in DRKS:
2024-01-19
Last update in DRKS:
2024-04-02
Registration type:
Prospective

Acronym/abbreviation of the study

ADHD-EMOTION

URL of the study

No Entry

Brief summary in lay language

Adults with ADHD (attention deficit hyperactivity disorder) are not diagnosed or are diagnosed too late. There are several reasons for this: ADHD often co-occurs with other mental health problems, there are no clear physical signs for a diagnosis, and a large proportion of adults with ADHD have difficulty controlling their emotions - up to 70%. Although difficulty managing emotions is not an official part of an ADHD diagnosis, there is some evidence that it should be considered as a separate subtype when diagnosing ADHD. The way ADHD shows up in people and how well ADHD medications work suggests that a specific molecule in the brain called the "norepinephrine transporter (NET)" may play a role in the development of ADHD. The study will investigate whether NET levels are different in adults with ADHD who have difficulty controlling their emotions compared to adults with other manifestations of ADHD. In addition, we will investigate whether these concentrations are related to ADHD symptom severity and brain functioning.

Brief summary in scientific language

The diagnosis of ADHD in adults is often not made or made too late. Reasons for this are the frequent comorbidity with other mental illnesses, the lack of diagnostic biomarkers and the fact that up to 70% of adults with ADHD suffer from difficulties in emotion regulation. Emotional dysregulation (ED) is not a diagnostic criterion for ADHD. However, there is evidence that it should be considered as part of the diagnosis and classified as a independent subtype. The clinical presentation of ADHD and the efficacy of ADHD-specific medication suggest the involvement of the noradrenaline transporter (NET) in the pathogenesis of ADHD. The aim of the study is to demonstrate and quantify in vivo the central NET availability in adults with ADHD of the emotionally dysregulated presentation type compared to individuals with other ADHD presentation types and to correlate it with the severity of ADHD symptomatology as well as with neuropsychological and neurophysiological parameters and functional networks.

Health condition or problem studied

ICD10:
F90.0 - Disturbance of activity and attention
Healthy volunteers:
No

Interventions, Observational Groups

Arm 1:
Participants with emotionally dysregulated presentation of ADHD form the observation group (BG). On the first day of the study, after enrolment and checking the inclusion and exclusion criteria, the BG undergoes various procedures to assess the severity of ADHD symptoms and to record neuropsychological and neurophysiological parameters, some of which are computer-assisted. On the second day of the study, a PET/MRI scan is used to visualise and quantify the availability of norepinephrine transporters (NETs) in brain regions associated with ADHD.
Arm 2:
Gender-matched participants with inattentive presentation of ADHD form the comparison group. After inclusion in the study, they undergo the same study procedure in the same time regime as the observation group.

Endpoints

Primary outcome:
The primary objective is to test the hypothesis that individuals with ADHD of the emotionally dysregulated presentation type differ in NET availability from individuals with other presentation types of ADHD. To determine central NET availability, acquired PET data will be reconstructed and corrected in a standardized manner. NET distribution volume (DVR)/binding potential (BP) images will be generated from the PET data using reference tissue models. Volumes of interest (VOI) are defined in the DVR images after coregistration of the parametric DVR images with the individual 3D MRI dataset, and the regional DVRs are determined. In addition to VOI-based analysis, other statistical evaluation methods are used, such as
Secondary outcome:
In particular, NET availability in brain regions relevant for response inhibition and impulse modulation will be compared between the observation groups. Furthermore, it will be investigated whether NET availability correlates with ADHD symptom severity, neuropsychological and neurophysiological parameters, and functional networks. a) DMS-ADHS total score and subscale scores from Conners’ Adult ADHD Rating Scales (CAARS) b) Clinical Global Impressions Scale of Severity score (CGI-S) c) Sum scores of functional level questionnaire categories d) Adult ADHD Quality of Life Questionnaire (AAQoL) total and subscale scores e) Trail Making Test Part B (TMT-B) performance times and error rates f) Mean, median and range of reaction times as well as correct responses, errors, omissions and missings of selected subtests (Working Memory, Divided Attention, Go/NoGo, Flexibility, Visual Scanning) of the Test Battery for Attention (TAP) g) the mean vigilance level and the arousal stability score of the resting EEG as well as the latencies and amplitudes of the event-related potential.

Study Design

Purpose:
Basic research/physiological study
Retrospective/prospective:
Prospective
Study type:
Non-interventional
Longitudinal/cross-sectional:
Cross-sectional study
Study type non-interventional:
No Entry

Recruitment

Recruitment Status:
Recruiting planned
Reason if recruiting stopped or withdrawn:
No Entry

Recruitment Locations

Recruitment countries:
  • Germany
Number of study centers:
Monocenter study
Recruitment location(s):
  • University medical center Klinik und Poliklinik für Psychiatrie und Psychotherapie 04103 Leipzig

Recruitment period and number of participants

Planned study start date:
2024-06-01
Actual study start date:
No Entry
Planned study completion date:
2024-12-31
Actual Study Completion Date:
No Entry
Target Sample Size:
40
Final Sample Size:
No Entry

Inclusion Criteria

Sex:
All
Minimum Age:
18 Years
Maximum Age:
35 Years
Additional Inclusion Criteria:
Signed informed consent for study participation, Confirmed primary diagnosis of adult ADHD according to DSM-5, Medication naïve or with previous use of psychostimulants, antidepressants, or atomoxetine after a 4-week washout period of the respective medication, Ability to perform a computerized neurobiological test battery, Sufficient understanding of the German language, Consent according to §7 Abs.2 Nr.15 of the GCP regulation about the passing on of the pseudonymized data in the context of the documentation and notification duties according to §12 and §13 GCP regulation.

Exclusion Criteria

Lack of capacity to consent, Acute suicidality, Current depressive disorder, single or recurrent episode, Emotionally unstable personality disorder, borderline type, Schizophrenia spectrum and other psychotic disorders, Bipolar and related disorders, Alcohol and/or drug dependence as a primary diagnosis and/or a positive urine drug screen, Mental disorders with a known physiological etiology, Intelligence deficits, Treatment with a neurostimulation procedure within the past 6 months, Contraindications to PET or MRI scan, Severe somatic or neurological comorbidity or unstable clinical condition within the past 12 months that affects cognitive performance, Caregiving and/or institutionalization, Pregnancy or positive urine pregnancy test, lactation. Lack of compliance

Addresses

Primary Sponsor

Address:
Universität Leipzig
Ritterstraße 26
04109 Leipzig
Germany
Telephone:
No Entry
Fax:
No Entry
Contact per E-Mail:
Contact per E-Mail
URL:
No Entry
Investigator Sponsored/Initiated Trial (IST/IIT):
Yes

Contact for Scientific Queries

Address:
Universität Leipzig, Medizinische Fakultät, Klinik und Poliklinik für Psychiatrie und Psychotherapie
Prof. Dr. med. Maria Strauß
Semmelweisstraße 10, Haus 13
04103 Leipzig
Germany
Telephone:
+49 341 97 24334
Fax:
-49 341 97 24509
Contact per E-Mail:
Contact per E-Mail
URL:
https://www.uniklinikum-leipzig.de/einrichtungen/psychiatrie-psychotherapie

Contact for Public Queries

Address:
Universität Leipzig, Medizinische Fakultät, Klinik und Poliklinik für Psychiatrie und Psychotherapie
Dipl.-Psych. Nicole Mauche
Semmelweisstraße 10, Haus 13
04103 Leipzig
Germany
Telephone:
+49 341 97 24430
Fax:
+49 341 97 24579
Contact per E-Mail:
Contact per E-Mail
URL:
https://www.uniklinikum-leipzig.de/einrichtungen/psychiatrie-psychotherapie

Principal Investigator

Address:
Universität Leipzig, Medizinische Fakultät, Klinik und Poliklinik für Psychiatrie und Psychotherapie
Prof. Dr. med. Maria Strauß
Semmelweisstraße 10, Haus 13
04103 Leipzig
Germany
Telephone:
+49 341 97 24334
Fax:
-49 341 97 24509
Contact per E-Mail:
Contact per E-Mail
URL:
https://www.uniklinikum-leipzig.de/einrichtungen/psychiatrie-psychotherapie

Sources of Monetary or Material Support

Private sponsorship (foundations, study societies, etc.)

Address:
Roland-Ernst-Stiftung
Naumannstraße 8
01309 Dresden
Germany
Telephone:
+49 351 545 159 17
Fax:
+49 351 656 159 18
Contact per E-Mail:
Contact per E-Mail
URL:
https://roland-ernst-stiftung.com/

Ethics Committee

Address Ethics Committee

Address:
Ethik-Kommission an der Medizinischen Fakultät der Universität Leipzig
Liebigstraße 18
04103 Leipzig
Germany
Telephone:
+49-341-9715490
Fax:
No Entry
Contact per E-Mail:
Contact per E-Mail
URL:
http://www.uniklinikum-leipzig.de/einrichtungen/ethik-kommission

Vote of leading Ethics Committee

Vote of leading Ethics Committee
Date of ethics committee application:
2023-09-04
Ethics committee number:
322/23-ek
Vote of the Ethics Committee:
Approved
Date of the vote:
2024-01-17

Further identification numbers

Other primary registry ID:
No Entry
EudraCT Number:
No Entry
UTN (Universal Trial Number):
No Entry
EUDAMED Number:
No Entry

IPD - Individual Participant Data

Do you plan to make participant-related data (IPD) available to other researchers in an anonymized form?:
Yes
IPD Sharing Plan:
After publication of the main results, and upon justified request by researchers conducting a meta-analysis with individual patient data, the individual patient data underlying the published results will be shared after de-identification. This requires approval from the local ethics committee of the investigator requesting the data and public registration of the meta-analysis. Summary statistics beyond the scope of the published data will be made available to researchers upon reasonable request for meta-analyses, unless the required data analysis is unreasonably time-consuming. The full study protocol and statistical analysis plan will be made publicly available with the publication of the main results.

Study protocol and other study documents

Study protocols:
No Entry
Study abstract:
No Entry
Other study documents:
No Entry
Background literature:
No Entry
Related DRKS studies:
No Entry

Publication of study results

Planned publication:
No Entry
Publikationen/Studienergebnisse:
No Entry
Date of first publication of study results:
No Entry
DRKS entry published for the first time with results:
No Entry

Basic reporting

Basic Reporting / Results tables:
No Entry
Brief summary of results:
No Entry