Evaluation of Brain Neurotransmitter Levels in Adults With ADHD, Before and After Stimulant Treatment (ADHD)

July 11, 2024 updated by: Weizmann Institute of Science

Measuring Glutamate and GABA Brain Levels in Adults With Attention Deficit Hyperactivity Disorder (ADHD) Using Magnetic Resonance Spectroscopy (MRS)

Background:

Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent neurobiological brain disorders. Diagnosis of ADHD in adults is complex and subjective. Recent studies give further support for the involvement of glutamatergic and GABAergic neurotransmitters in the pathophysiology of ADHD. Studies show that glutamate (Glu) and GABA change according to stimulant treatment. Measuring modulations in the anterior cingulate cortex (ACC) of Glu and GABA may help to explore the pathophysiology of ADHD and give a diagnostic biomarker tool for ADHD in adults.

Aim:

To characterize Glu and GABA levels in the ACC, by using the proton Magnetic Resonance Spectroscopy ([1H]MRS) system in adults with ADHD compared to healthy control subjects (HCS), before and after stimulant treatment, and to correlate between Glu and GABA levels and clinical symptoms.

Method:

ADHD adults ages 18-40 years (N= 35), and HCS (N= 25), will fill out a DSMV and ASRS questionnaire.

Spectroscopic analyses will be done using 1H MRS (3T) in ADHD adults, before and after stimulant treatment (Methylphenidate /Mixed Amphetamine salts) in an open-label fashion as compared to HCS. Proton spectra will be acquired from the ACC.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Hypothesis:

  1. We hypothesize that brain Glu and GABA levels and/or their ratio involved in ADHD pathology
  2. Glu and GABA levels and/or their ratio will be affected by medical treatment in ADHD group
  3. Alteration of Glu and GABA and/or their ratios, before and after treatment, will correlate with clinical response to treatment

Primary Objectives:

To characterize changes in Glu and GABA levels in the ACC of adults with ADHD compared to the healthy subjects To characterize Glu and GABA levels in the ACC of adults with ADHD before and 1.5 hrs. after stimulant treatment using 1H MRS system.

Secondary objective:

To study the correlation between Glu and GABA levels in ADHD patients (before and after medical treatment) and clinical symptoms as assessed by ASRS and DSMV and/or NeuroTrax Braincare computerized test

Design and study population:

This is a prospective observational, open-label, comparative study that is approved by the Institutional Review Board (IRB) of Maccabi Healthcare services and the Ethical Committee of Tel Aviv University, in collaboration with the Weizmann Institute of Science. Medically healthy ADHD adults of ages 18-40 years (N= 35), and matched HCS (N= 25) will be recruited.

Procedure ADHD Participants will be enrolled from the Maccabi database. Volunteers will be enrolled as a Control group

  • Pre-assessment questionnaires including epidemiologic data, DSMV, and Adult ADHD Self-Report Scale (ASRS) will be filled out.
  • Detailed explanation will be given of the trial objectives, trial methods and risks or possible discomfort that may result from an MRI/MRS examination
  • During screening, subjects will receive information regarding the study, including general eligibility criteria, study design, procedures and duration. Subjects will have the opportunity to ask questions and will undergo an informed consent procedure. Subjects meeting inclusion/exclusion criteria will be enrolled. The participant will sign an informed consent form and will receive a copy.

After screening, participants who meet the inclusion criteria will be invited to the center for Computational Neuroimaging at Weizmann Institute of Science to perform the MRS scan.

ADHD patients will be instructed not to take medication for at least 72 hours prior to their arrival and will be asked to bring their medical drug treatment.

All participants will go through spectroscopic analyses using 1H MRS (at 3 Tesla) Control group participants will go through MRS once and complete their study. Adults with ADHD will repeat MRS screening, 1.5 hours after taking their medical treatment (Methylphenidate /Mixed Amphetamine salts).

Study population:

Medically healthy adults diagnosed with ADHD (men and women) ages 18-40 years (N= 35), treated with Amphetamines (Mixed Amphetamine salts (Attent) or short-acting methylphenidate (Ritalin)) will be enrolled from the Maccabi database. Matched HCS (N= 25) volunteers ages 18-40 years, who did not report ADHD or any other illness or medical conditions, and who do not take chronic medications, will be enrolled from the general population.

The Adult ADHD Self-Report Scale and DSMV questionnaire will be used to determine ADHD symptoms in both groups.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Israel
      • Kfar Saba, Israel
        • Maccabi health services
      • Reẖovot, Israel
        • Weizmann

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 36 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

Giving informed written consent to participate on a voluntary basis.

For the healthy control group:

Men and women aged 18-40 years, who did not report ADHD or any other chronic or psychiatric illness or medical conditions (at most two symptoms of inattention and/or hyperactivity/impulsivity).

For the ADHD group patients:

  1. Men and women aged 18-40 years, who have a diagnosis of ADHD, according to DSM V criteria by a Neurologist.
  2. Have a valid prescription for Mixed Amphetamine salts (Attent) or short-acting methylphenidate (Ritalin) for ADHD
  3. Withhold medication 72h prior to MRS scan.

Exclusion Criteria:

Exclusion criteria identical for patients and control group:

  1. Subjects with metallic devices that precludemagnetic resonance imaging or any silver part that is not MRI compliant
  2. Current presence of any other DSM V psychiatric disorder
  3. Significant medical or neurological illness affecting brain function
  4. Subjects with any clinically significant or unstable medical conditions
  5. Use of any psychotropic medication, other than stimulants, in the previous 3 months
  6. Pregnant women
  7. BMI > 35
  8. History of brain MRI
  9. A patient who does not agree that the scan will be decoded by a radiologist
  10. A patient who does not agree that in case of an abnormal finding, the imaging results will be forwarded to the attending physician for further clarification
  11. Understanding and/or language problems

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Medically healthy adults diagnosed with ADHD
Medically healthy adults diagnosed with ADHD (men and women) ages 18-40 years (N= 35), treated with Amphetamines (Mixed Amphetamine salts (Attent) or short-acting methylphenidate (Ritalin)
Other: Neurotransmitters evaluation by MRS
Baseline MRS screening for volunteers and ADHD groups and repeated measurement for ADHD group after taking stimulant drug treatment
No Intervention: Control
HCS (N= 25) volunteers ages 18-40 years, who did not report ADHD or any other illness or medical conditions, and who do not take chronically medications, will be enrolled from the general population.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Glu and GABA levels measured by MRS in ACC brain area
Time Frame: 72 hours without stimulant
Differences in levels of Glu and GABA in ADHD patients compared to healthy volunteers
72 hours without stimulant
Glu and GABA levels measured by MRS in ACC brain area before and after medical treatment
Time Frame: 90 minutes after stimulant
Differences in levels of Glu and GABA measured before and after medical treatment.
90 minutes after stimulant

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Correlation of Glu and GABA levels with clinical symptoms before and after stimulants
Time Frame: 210 minutes after stimulant
Analysis of correlation of Glu and GABA levels with post/previous clinical manifestation evaluated by Neuro Trax Braincare test and/or ASRS and DSMV questionnaire.
210 minutes after stimulant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Weizmann Institute of Science

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Tel Aviv University
Maccabi Healthcare Services, Israel

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Assaf Tal, PhD., Maccabi Healthcare Services, Israel

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 11, 2024

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 11, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 11, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 25, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 25, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 30, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 15, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 11, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 0109-19-MOH

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Sharing of data generated by this project is an essential part of our proposed activities and will be carried out in several different ways. We would wish to make our results available both to the community of scientists interested in ADHD and the biology to avoid unintentional duplication of research. Conversely, we would welcome collaboration with others who could make use of the H-MRS protocols developed in psychiatric disease. Any patient-level data that is shared will be anonymized to protect personally identifiable information.

IPD Sharing Time Frame

4 years

IPD Sharing Access Criteria

Broad sharing of the data will be communicated through NDA and its support staff according to the Provisions for Data Submission and Data Sharing Schedule. The findings of this research will be de-identified data, such that the identities of participants cannot be readily ascertained or otherwise associated with the data by NDA staff or secondary data users.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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