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

NCT04823364 | Terminated

• 1 other identifier: 0109-19-MOH
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Attention Deficit Disorder With Hyperactivity

Keywords

ACC; methylphenidate; MRS; Glutamate; GABA

Outcome Measures

Primary Outcomes (2)

• Glu and GABA levels measured by MRS in ACC brain area

  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

  Differences in levels of Glu and GABA measured before and after medical treatment.

  90 minutes after stimulant

Secondary Outcomes (1)

• Correlation of Glu and GABA levels with clinical symptoms before and after stimulants

  210 minutes after stimulant

Study Arms (2)

Medically healthy adults diagnosed with ADHD

ACTIVE COMPARATOR

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

Control

NO INTERVENTION

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.

Interventions

Neurotransmitters evaluation by MRS OTHER

Baseline MRS screening for volunteers and ADHD groups and repeated measurement for ADHD group after taking stimulant drug treatment

Medically healthy adults diagnosed with ADHD

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• Subjects with metallic devices that precludemagnetic resonance imaging or any silver part that is not MRI compliant
• Current presence of any other DSM V psychiatric disorder
• Significant medical or neurological illness affecting brain function
• Subjects with any clinically significant or unstable medical conditions
• Use of any psychotropic medication, other than stimulants, in the previous 3 months
• Pregnant women
• BMI \> 35
• History of brain MRI
• A patient who does not agree that the scan will be decoded by a radiologist
• 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
• Understanding and/or language problems

Sponsors & Collaborators

• Weizmann Institute of Science: lead
• Tel Aviv University: collaborator
• Maccabi Healthcare Services, Israel: collaborator

Study Sites (2)

Maccabi Health Services

Kfar Saba, Israel

Location

Weizmann

Rehovot, Israel

Location

Related Publications (7)

• Naaijen J, Lythgoe DJ, Amiri H, Buitelaar JK, Glennon JC. Fronto-striatal glutamatergic compounds in compulsive and impulsive syndromes: a review of magnetic resonance spectroscopy studies. Neurosci Biobehav Rev. 2015 May;52:74-88. doi: 10.1016/j.neubiorev.2015.02.009. Epub 2015 Feb 21.

  PMID: 25712432 BACKGROUND

• Maltezos S, Horder J, Coghlan S, Skirrow C, O'Gorman R, Lavender TJ, Mendez MA, Mehta M, Daly E, Xenitidis K, Paliokosta E, Spain D, Pitts M, Asherson P, Lythgoe DJ, Barker GJ, Murphy DG. Glutamate/glutamine and neuronal integrity in adults with ADHD: a proton MRS study. Transl Psychiatry. 2014 Mar 18;4(3):e373. doi: 10.1038/tp.2014.11.

  PMID: 24643164 BACKGROUND

• Ende G, Cackowski S, Van Eijk J, Sack M, Demirakca T, Kleindienst N, Bohus M, Sobanski E, Krause-Utz A, Schmahl C. Impulsivity and Aggression in Female BPD and ADHD Patients: Association with ACC Glutamate and GABA Concentrations. Neuropsychopharmacology. 2016 Jan;41(2):410-8. doi: 10.1038/npp.2015.153. Epub 2015 Jun 4.

  PMID: 26040503 BACKGROUND

• Bauer J, Werner A, Kohl W, Kugel H, Shushakova A, Pedersen A, Ohrmann P. Hyperactivity and impulsivity in adult attention-deficit/hyperactivity disorder is related to glutamatergic dysfunction in the anterior cingulate cortex. World J Biol Psychiatry. 2018 Oct;19(7):538-546. doi: 10.1080/15622975.2016.1262060. Epub 2016 Dec 15.

  PMID: 27973969 BACKGROUND

• Perlov E, Philipsen A, Hesslinger B, Buechert M, Ahrendts J, Feige B, Bubl E, Hennig J, Ebert D, Tebartz van Elst L. Reduced cingulate glutamate/glutamine-to-creatine ratios in adult patients with attention deficit/hyperactivity disorder -- a magnet resonance spectroscopy study. J Psychiatr Res. 2007 Dec;41(11):934-41. doi: 10.1016/j.jpsychires.2006.12.007. Epub 2007 Feb 15.

  PMID: 17303167 BACKGROUND

• Endres D, Perlov E, Maier S, Feige B, Nickel K, Goll P, Bubl E, Lange T, Glauche V, Graf E, Ebert D, Sobanski E, Philipsen A, Tebartz van Elst L. Normal Neurochemistry in the Prefrontal and Cerebellar Brain of Adults with Attention-Deficit Hyperactivity Disorder. Front Behav Neurosci. 2015 Sep 28;9:242. doi: 10.3389/fnbeh.2015.00242. eCollection 2015.

  PMID: 26441572 BACKGROUND

• Bezalel V, Paz R, Tal A. Inhibitory and excitatory mechanisms in the human cingulate-cortex support reinforcement learning: A functional Proton Magnetic Resonance Spectroscopy study. Neuroimage. 2019 Jan 1;184:25-35. doi: 10.1016/j.neuroimage.2018.09.016. Epub 2018 Sep 7.

  PMID: 30201464 BACKGROUND

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Study Officials

• Assaf Tal, PhD.

  Maccabi Healthcare Services, Israel

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: No masking
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Group 1 control healthy people Group 2 ADHD

Study Record Dates

• First Submitted: March 25, 2021
• First Posted: March 30, 2021
• Study Start: July 11, 2024
• Primary Completion: July 11, 2024
• Study Completion: July 11, 2024
• Last Updated: July 15, 2024

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: 4 years
• 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.

Locations

IL (2)