Attention Deficit Hyperactivity DisorderNCT04326543
Temperament Dimensions and Awakening Salivary Cortisol Levels in ADHD.
An observational study of Attention Deficit Hyperactivity Disorder, run by Università degli Studi di Sassari at 2 sites in Italy.
Trial summary
To analyze heterogeneity in ADHD experts in last decade advised to look beyond the lists of existing symptoms towards phenotypic measures that can be represented dimensionally and have well-theorized relationships with neurobiological systems, (Sonuga-Barke \& Halperin, 2010; Insel et al, 2010; Fair D, Bathula D… Read more about this study
- Who is it for?
- Ages 3 to 16 yearsHealthy volunteers can take part
- Conditions the study is for
- Attention Deficit Hyperactivity Disorder
- What is being tested?
- Swanson, Noolan and Phelham - IV edition (SNAP-IV); Conners' Parent Rating Scales (CPRS)
- Type of treatment
- Injection or infusion
- How many people
- 120 participants
- Where
- 2 sitesItaly
- Study dates
- 18 Jan 2017to 12 Jan 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 16 years
- All sexes
- Healthy volunteers accepted
- Child
Study population: We enrolled 67 individuals with ADHD and 70 typically developing youths (TDY) aged between 4 and 16 years. Individuals with ADHD were recruited from the Child and Adolescent Neuropsychiatry Unit, University of Sassari, Italy.
Who may be able to join
- ADHD group:
- The assessment was completed as part of their routine psychiatric assessment using unstructured interview, screening of ADHD and other psychiatric symptoms through parent questionnaires, and direct observation with the participants, which led to a DSM-5-based diagnosis of ADHD;
- Signed informed consent from parents or legal guardian and/or assent for youth aged >12 y/o.
- TDY (Typically Developing Control) - group:
- Signed informed consent from parents or legal guardian and/or assent for youth aged >12 y/o;
- TDY were recruited from pre-school, primary and secondary schools in the local catchment area.
- Assessment of the TDY was carried out by a clinician in schools through an unstructured interview with the parents and teachers.
Who cannot join
- ADHD group:
- Not signed informed consent from parents or legal guardian and/or assent for youth aged >12 y/o;
- IQ below 70;
- neurological and other psychiatric disorders;
- genetic and/or medical conditions mimicking ADHD symptoms;
- treatment with psychotropic medications other than ADHD medications;
Show all 13Show fewer
- TDY were also excluded if they presented with any learning or behavioural difficulties as reported in the parent and teacher interviews, as well as mild, moderate or severe symptoms of ADHD in the clinician-led rating scale.
- TDY (Typically Developing Control) - group:
- Not signed informed consent from parents or legal guardian and/or assent for youth aged >12 y/o;
- IQ below 70;
- neurological and other psychiatric disorders;
- genetic and/or medical conditions mimicking ADHD symptoms;
- treatment with psychotropic medications other than ADHD medications.
Trial locations and contacts
2 sites in 1 country.
Italy2 sites
Alessandra Carta
Sassari, 07100
Complex Operating Unit of Child and Adolescent Neuropsychiatry - University of Sassari
Sassari, 07100
About this study
Official title: Association Between Temperament Dimensions and Awakening Salivary Cortisol Levels in Children and Adolescents With Attention Deficit Hyperactivity/Impulsivity Disorder (ADHD)
To analyze heterogeneity in ADHD experts in last decade advised to look beyond the lists of existing symptoms towards phenotypic measures that can be represented dimensionally and have well-theorized relationships with neurobiological systems, (Sonuga-Barke \& Halperin, 2010; Insel et al, 2010; Fair D, Bathula D, Nikolas M, Nigg JT, 2012; Georgiades S, Szatmari P, Boyle M, 2013; Sanislow CA, Pine DS, Quinn KJ, et al, 2013). This is the nucleus of RDoC aims because children and adolescents with ADHD can be characterized in terms of several features that are best represented as dimensions and have well-theorized relationships to biological systems (Cuthbert \& Insel, 2013).
Read the detailed description
Recently evidence suggests that measures of child temperament may predict ADHD symptoms (Einziger et al., 2018). Temperament is a characteristic of personality (Buss \& Plomin, 1984; Crowell, 2016) and refers to individual, neurobiologically-based difference in reactivity, self-regulation and cognition (Eisenberg, 2012).
It has been previously emphasized (Nigg J., 2016), that Hypotalamic-Pituitary-Adrenal (HPA) axis, through the cortisol hormone, may represent a powerful biological measure of behavioural self-regulatory systems, activity level, cognition, temperament (Stadler et al, 2011; Martel et al., 2009; Sonuga-Barke, 2005) and arousal (Snoek, Van Goozen, Matthys, Buitelaar, \& Engeland, 2004). Cortisol is released from the surrenal gland by means of the HPA axis activation, in response to catecholaminergic neurotransmitters (Ulrich-Lai \& Herman, 2009). Cortisol is involved in the regulation of a wide range of body functions, including emotion processing (Skosnik, Chatterton, Swisher, \& Park, 2000), awakening (Fries, Dettenborn, \& Kirschbaum, 2009) and stress responses (Chrousos, Kino, \& Charmandari, 2009).
Both cortisol and temperament may share self-response regulatory processes (Martel et al., 2008; Nigg, 2016; Ulrich-Lai \& Herman, 2009), and one study on 70 healthy pre-schoolers indicates that children with SE temperament has higher morning salivary cortisol levels during their first week of a new primary school year (Davis, Donzella, Krueger, \& Gunnar, 1999), hypothesized as a stress-induced effect.
To date, no studies have been conducted to study heterogeneity starting from the self-response regulatory processes between temperament and cortisol in children and adolescents with ADHD.
As for clinical application of HPA-axis and cortisol level in ADHD diagnosis and dimension, available studies are, as yet, either inconsistent (Bonvicini, Faraone, \& Scassellati, 2016; Freitag et al, 2009, Corominas et al, 2012) or suggestive, but not significant, upon dimensional stratification of ADHD symptoms (Pinto et al., 2016).
The aims of this study to contribute to the issue of clinical heterogeneity of ADHD, analysing whether ADHD symptoms and co-morbidity traits simultaneously link to both cortisol level and temperament dimensions, as biomarkers of arousal and inhibited behaviour. To pursue our aim we formulated five specific research questions: i) Do temperament dimensions and awakening cortisol level differ between children and adolescents with ADHD and TDC? ii) Do temperament dimensions and awakening cortisol levels correlate with dimension of ADHD core symptoms? iii) Does awakening cortisol level associate with any of the three-temperament dimension? iv) Do parent ratings of the oppositional and defiant traits and anxiety traits affect the association between temperament dimensions and cortisol levels with ADHD core symptoms in the ADHD group?
- Conditions
- Attention Deficit Hyperactivity Disorder
- Being tested
- Swanson, Noolan and Phelham - IV edition (SNAP-IV); Conners' Parent Rating Scales (CPRS)
- Medical subject headings
- Attention Deficit Disorder with Hyperactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Swanson, Noolan and Phelham - IV edition (SNAP-IV); Conners' Parent Rating Scales (CPRS)Diagnostic test
Also called Rothbart Temperament questionnaires
- Ratings on the Swanson, Nolan and Pelham Evaluation Scale - IV (Bussing et al., 2008), were assessed during baseline visit for participants at the time of research assessment, to exclude the presence of ADHD symptoms in the healthy subjects. This scale is composed of 26 items for ADHD symptoms and ODD and was administered at baseline and at follow-up visit.
- Temperament assessment: we used the Mary Rothbart's Temperament Questionnaire, a caregivers' report measure designed to provide a detailed assessment of temperament.
- ADHD Rating scales: the Long Version of Conners' Parent Rating Scale (Conners et al., 1998) was used to quantify ADHD comorbidity symptoms, as ODD and Anxiety traits, in the children and adolescents with ADHD.
- Salivary cortisol: Sampling was performed during one ordinary weekday between 7 and 8 o'clock, within 60' after nocturnal awakening.
| Study group | Role | What they receive |
|---|---|---|
| ADHD and typically developing controls | 120 subject: 53 with an ADHD clinical diagnosis and 57 typically developing controls aged between 3 and 16 years old. Receives: Diagnostic Test: Swanson, Noolan and Phelham - IV edition (SNAP-IV); Conners' Parent Rating Scales (CPRS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
To examine the association of ADHD with temperament dimensions and low cortisol levels, building on previous research that these may represent potential markers of low behaviour inhibition and under-arousal in the disorder.
Specifically:
- we first investigate whether temperament dimensions and awakening cortisol level differ between youths with ADHD and controls and correlate with ADHD symptoms (inattention and hyperactivity-impulsivity).
- Second, we examine whether the three temperament dimensions are associated with awakening cortisol levels.
Measured: six months
To evaluate the association between cortisol levels and co-morbidity severity symptoms.
We test the association of oppositional-defiant and anxiety traits with the temperament dimensions and cortisol levels, and whether the association of ADHD with each temperament or cortisol measure remains when controlling for these comorbid psychiatric traits.
Measured: six months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2020
- Study start18 Jan 2017
- Primary completion29 Sep 2017
- Study completion12 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Attention Deficit Hyperactivity DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Università degli Studi di Sassari
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, ALESSANDRA CARTA, Università degli Studi di Sassari
- Investigators
- ALESSANDRA CARTA, Principal investigator, Sassari University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04326543
- Sponsor's protocol ID
- 2472/CE
- Status last verified
- Mar 2020
- First submitted
- 25 Mar 2020
- Last updated
- 30 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Statistical Analyses were performed using the software R (version R 3.4.1). Analysis of variance covaring for sex (ANCOVA) was used to compare the two groups on the three temperament dimensions and on the awakening cortisol levels. A series of linear regression model analyses were used to test the association of temperament dimensions and cortisol levels with ADHD traits and the oppositional-defiant and anxiety traits. To test the difference between cortisol levels on- and off- methylphenidate treatment in participants with ADHD, we performed repeated measures analysis of variance. Before analysis, cortisol levels were log-transformed to normal. Analyses were then carried out using standardized scores for all measures.
Publications
Karalunas SL, Fair D, Musser ED, Aykes K, Iyer SP, Nigg JT. Subtyping attention-deficit/hyperactivity disorder using temperament dimensions: toward biologically based nosologic criteria. JAMA Psychiatry. 2014 Sep;71(9):1015-24. doi: 10.1001/jamapsychiatry.2014.763.
PubMed 25006969Karalunas SL, Fair D, Musser ED, Aykes K, Iyer SP, Nigg JT. Notice of Retraction and Replacement. Karalunas et al. Subtyping attention-deficit/hyperactivity disorder using temperament dimensions: toward biologically based nosologic criteria. JAMA Psychiatry. 2014;71(9):1015-1024. JAMA Psychiatry. 2018 Apr 1;75(4):408-409. doi: 10.1001/jamapsychiatry.2018.0013. No abstract available.
PubMed 29516086Isaksson J, Nilsson KW, Nyberg F, Hogmark A, Lindblad F. Cortisol levels in children with attention-deficit/hyperactivity disorder. J Psychiatr Res. 2012 Nov;46(11):1398-405. doi: 10.1016/j.jpsychires.2012.08.021. Epub 2012 Sep 10.
PubMed 22974590
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Association Between Temperament Dimensions and Awakening Salivary Cortisol Levels in Children and Adolescents With Attention Deficit Hyperactivity/Impulsivity Disorder (ADHD)
- ClinicalTrials.gov ID
- NCT04326543
- Acronym / sponsor ID
- 2472/CE
- Conditions
- Attention Deficit Hyperactivity Disorder
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Università degli Studi di SassariUniversity, hospital or other
- Study start
- 18 Jan 2017 (actual)
- Primary completion
- 29 Sep 2017 (actual)
- Study completion
- 12 Jan 2018 (actual)
- First posted
- 30 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To analyze heterogeneity in ADHD experts in last decade advised to look beyond the lists of existing symptoms towards phenotypic measures that can be represented dimensionally and have well-theorized relationships with neurobiological systems, (Sonuga-Barke \& Halperin, 2010; Insel et al, 2010; Fair D, Bathula D, Nikolas M, Nigg JT, 2012; Georgiades S, Szatmari P, Boyle M, 2013; Sanislow CA, Pine DS, Quinn KJ, et al, 2013). This is the nucleus of RDoC aims because children and adolescents with ADHD can be characterized in terms of several features that are best represented as dimensions and have well-theorized relationships to biological systems (Cuthbert \& Insel, 2013).
Detailed description
Recently evidence suggests that measures of child temperament may predict ADHD symptoms (Einziger et al., 2018). Temperament is a characteristic of personality (Buss \& Plomin, 1984; Crowell, 2016) and refers to individual, neurobiologically-based difference in reactivity, self-regulation and cognition (Eisenberg, 2012).
It has been previously emphasized (Nigg J., 2016), that Hypotalamic-Pituitary-Adrenal (HPA) axis, through the cortisol hormone, may represent a powerful biological measure of behavioural self-regulatory systems, activity level, cognition, temperament (Stadler et al, 2011; Martel et al., 2009; Sonuga-Barke, 2005) and arousal (Snoek, Van Goozen, Matthys, Buitelaar, \& Engeland, 2004). Cortisol is released from the surrenal gland by means of the HPA axis activation, in response to catecholaminergic neurotransmitters (Ulrich-Lai \& Herman, 2009). Cortisol is involved in the regulation of a wide range of body functions, including emotion processing (Skosnik, Chatterton, Swisher, \& Park, 2000), awakening (Fries, Dettenborn, \& Kirschbaum, 2009) and stress responses (Chrousos, Kino, \& Charmandari, 2009).
Both cortisol and temperament may share self-response regulatory processes (Martel et al., 2008; Nigg, 2016; Ulrich-Lai \& Herman, 2009), and one study on 70 healthy pre-schoolers indicates that children with SE temperament has higher morning salivary cortisol levels during their first week of a new primary school year (Davis, Donzella, Krueger, \& Gunnar, 1999), hypothesized as a stress-induced effect.
To date, no studies have been conducted to study heterogeneity starting from the self-response regulatory processes between temperament and cortisol in children and adolescents with ADHD.
As for clinical application of HPA-axis and cortisol level in ADHD diagnosis and dimension, available studies are, as yet, either inconsistent (Bonvicini, Faraone, \& Scassellati, 2016; Freitag et al, 2009, Corominas et al, 2012) or suggestive, but not significant, upon dimensional stratification of ADHD symptoms (Pinto et al., 2016).
The aims of this study to contribute to the issue of clinical heterogeneity of ADHD, analysing whether ADHD symptoms and co-morbidity traits simultaneously link to both cortisol level and temperament dimensions, as biomarkers of arousal and inhibited behaviour. To pursue our aim we formulated five specific research questions: i) Do temperament dimensions and awakening cortisol level differ between children and adolescents with ADHD and TDC? ii) Do temperament dimensions and awakening cortisol levels correlate with dimension of ADHD core symptoms? iii) Does awakening cortisol level associate with any of the three-temperament dimension? iv) Do parent ratings of the oppositional and defiant traits and anxiety traits affect the association between temperament dimensions and cortisol levels with ADHD core symptoms in the ADHD group?
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ADHD and typically developing controls | – | Diagnostic Test: Swanson, Noolan and Phelham - IV edition (SNAP-IV); Conners' Parent Rating Scales (CPRS)120 subject: 53 with an ADHD clinical diagnosis and 57 typically developing controls aged between 3 and 16 years old. |
Who may qualify
- Ages
- 3 to 16 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- We enrolled 67 individuals with ADHD and 70 typically developing youths (TDY) aged between 4 and 16 years. Individuals with ADHD were recruited from the Child and Adolescent Neuropsychiatry Unit, University of Sassari, Italy.
Key inclusion criteria (7 listed)
- ADHD group:
- TDY (Typically Developing Control) - group:
Key exclusion criteria (13 listed)
- ADHD group:
- TDY (Typically Developing Control) - group:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Swanson, Noolan and Phelham - IV edition (SNAP-IV); Conners' Parent Rating Scales (CPRS)Also: Rothbart Temperament questionnaires* Ratings on the Swanson, Nolan and Pelham Evaluation Scale - IV (Bussing et al., 2008), were assessed during baseline visit for participants at the time of research assessment, to exclude the presence of ADHD symptoms in the healthy subjects. This scale is composed of 26 items for ADHD symptoms and ODD and was administered at baseline and at follow-up visit. * Temperament assessment: we used the Mary Rothbart's Temperament Questionnaire, a caregivers' report measure designed to provide a detailed assessment of temperament. * ADHD Rating scales: the Long Version of Conners' Parent Rating Scale (Conners et al., 1998) was used to quantify ADHD comorbidity symptoms, as ODD and Anxiety traits, in the children and adolescents with ADHD. * Salivary cortisol: Sampling was performed during one ordinary weekday between 7 and 8 o'clock, within 60' after nocturnal awakening. | Diagnostic test | ADHD and typically developing controls |
Primary outcome
To examine the association of ADHD with temperament dimensions and low cortisol levels, building on previous research that these may represent potential markers of low behaviour inhibition and under-arousal in the disorder.
Time frame: six months
Specifically: * we first investigate whether temperament dimensions and awakening cortisol level differ between youths with ADHD and controls and correlate with ADHD symptoms (inattention and hyperactivity-impulsivity). * Second, we examine whether the three temperament dimensions are associated with awakening cortisol levels.
To evaluate the association between cortisol levels and co-morbidity severity symptoms.
Time frame: six months
We test the association of oppositional-defiant and anxiety traits with the temperament dimensions and cortisol levels, and whether the association of ADHD with each temperament or cortisol measure remains when controlling for these comorbid psychiatric traits.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2020.
- Background: PubMed 25006969Karalunas SL, Fair D, Musser ED, Aykes K, Iyer SP, Nigg JT. Subtyping attention-deficit/hyperactivity disorder using temperament dimensions: toward biologically based nosologic criteria. JAMA Psychiatry. 2014 Sep;71(9):1015-24. doi: 10.1001/jamapsychiatry.2014.763.
- Results publication: PubMed 29516086Karalunas SL, Fair D, Musser ED, Aykes K, Iyer SP, Nigg JT. Notice of Retraction and Replacement. Karalunas et al. Subtyping attention-deficit/hyperactivity disorder using temperament dimensions: toward biologically based nosologic criteria. JAMA Psychiatry. 2014;71(9):1015-1024. JAMA Psychiatry. 2018 Apr 1;75(4):408-409. doi: 10.1001/jamapsychiatry.2018.0013. No abstract available.
- Results publication: PubMed 22974590Isaksson J, Nilsson KW, Nyberg F, Hogmark A, Lindblad F. Cortisol levels in children with attention-deficit/hyperactivity disorder. J Psychiatr Res. 2012 Nov;46(11):1398-405. doi: 10.1016/j.jpsychires.2012.08.021. Epub 2012 Sep 10.
- Individual participant dataSharing planned: No. Statistical Analyses were performed using the software R (version R 3.4.1). Analysis of variance covaring for sex (ANCOVA) was used to compare the two groups on the three temperament dimensions and on the awakening cortisol levels. A series of linear regression model analyses were used to test the association of temperament dimensions and cortisol levels with ADHD traits and the oppositional-defiant and anxiety traits. To test the difference between cortisol levels on- and off- methylphenidate treatment in participants with ADHD, we performed repeated measures analysis of variance. Before analysis, cortisol levels were log-transformed to normal. Analyses were then carried out using standardized scores for all measures.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
ALESSANDRA CARTA principal investigator
Sassari University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Attention Deficit Hyperactivity Disorder, run by Università degli Studi di Sassari at 2 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To examine the association of ADHD with temperament dimensions and low cortisol levels, building on previous research that these may represent potential markers of low behaviour inhibition and under-arousal in the disorder. (time frame: six months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04326543, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2020.