Type 1 DiabetesNCT02575001
The Influence of Psychobiological Adversity to Children and Adolescents With Type 1 Diabetes
An observational study of Type 1 Diabetes and Stress, run by University of Ljubljana, Faculty of Medicine at 1 site in Slovenia.
Trial summary
The aims of this study are two fold: To show whether there is an increased environmental or genetic susceptibility to stress in patients with T1D and whether it influences diabetes management. Read more about this study
- Who is it for?
- Ages 8 to 15 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 1 Diabetes, Stress
- What is being tested?
- Psychological background determinations, Genetic susceptibility determination and Cortisol release test
- Type of treatment
- Surgery or procedure, Lifestyle or therapy programme
- How many people
- 207 participants
- Where
- 1 siteSlovenia
- Study dates
- Jul 2015to Dec 2019
- 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 8 to 15 years
- All sexes
- Healthy volunteers accepted
- Child
Study population: Children of 8 to 15 years of age with type 1 diabetes with their parents; Healthy primary school pupils of 8 to 15 years of age with their parents
Who may be able to join
- Informed consent signed by a parent/legal guardian and informed assent signed by the study participant prior study entry
- Diagnosed with Type 1 DM prior to signature of Patient Informed Consent (PIC) (for the T1D group).
- Age between 8-15 years old (inclusive) at signature of PIC
- Treated by the investigator's centre prior signature of PIC (For the T1D group).
- Willing to undergo all study procedures
Who cannot join
- Any documented concomitant chronic disease known to affect diabetes control (e.g. altered renal function, active cancer undergoing treatment, Crohn's disease, ulcerative colitis, Mb Addison disease)
- Any other medical, social or psychological condition that, in the investigator's opinion, makes the patient unable to comply with the study protocol (e.g. intellectual disability).
Trial locations and contacts
1 site in 1 country.
About this study
The aims of this study are two fold: To show whether there is an increased environmental or genetic susceptibility to stress in patients with T1D and whether it influences diabetes management. And to develop a strategy for the assessment and treatment of patients with T1D and an increased risk for development of psychopathology under stress.
Read the detailed description
Lately, a marked increase in the incidence and earlier age of onset of type 1 diabetes (T1D) has been noted. These observations could also be connected to an increased prevalence of stressful experiences and a lowered stress tolerance in some children.
The way a person responds to stress is determined by the interplay of genetic and environmental factors. Environmental experiences at specific times of development have been shown to shape individual's hypothalamic-pituitary-adrenal axis (HPA axis) stress response. It is known, that early development of central nervous system is critically dependent on child's interaction with the environment (experience dependent maturation), especially to the attachment to caregivers (most often the mother). Appropriate caregiving is connected to lower basal cortisol levels in children and a more stable HPA axis response after the exposure to stress. Any circumstances that disturbed the formation of the attachment to the primary caregiver (e.g. complications at delivery, psychosocial stressors affecting the mother or mother's postpartum depression) resulted in higher HPA axis responsiveness to stress in the affected children.
Changes in individual genes have also been shown to influence a person's susceptibility to stress and risk for the development of stress-induced psychopathology.
- Conditions
- Type 1 Diabetes, Stress
- Being tested
- Psychological background determinations, Genetic susceptibility determination, Cortisol release test, Saliva cortisol measurement
- Keywords
- Type 1 diabetes, Children and adolescents, Stress, Genetic factors, Psychological background
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Psychological background determinationsBehavioural
For the psychological background determinations a structured interview and questionnaires will be administered:
- Child Attachment Interview (CAI)
- General/sociodemographic questionnaire with the questions on diabetes management, current health status and the child's development in the infancy
- "Parenting Stress Index" with the "19-item Life Stress Scale" (PSI)
- Achenbach System of Empirically Based Assessment (CBCL, YSR)
- Holmes and Rahe "Social readjustment rating scale"
- Lifetime Incidence of Traumatic Events (LITE) - parent and child reports of child's trauma/loss history (LITE- S/ P)
- Experiences in Close Relationships - Relationship Structures questionnaire (ECR-RS)
Genetic susceptibility determinationGenetic
DNA will be isolated from the patients' blood samples and form the control subjects buccal swabs. The genes with expected influence to stress reactivity and mental disorders will be tested.
Cortisol release testProcedure or surgery
Synacthen test - will be used with the group of patients with type 1 diabetes to measure HPA axis reactivity
Saliva cortisol measurementProcedure or surgery
Saliva cortisol measurement - will be used with the patients before and after the Synacthen test and with the Hashimoto thyroiditis and the healthy control group before and after the Child Attachment Interview
| Study group | Role | What they receive |
|---|---|---|
| Type 1 diabetes | Children with Type 1 diabetes, age from 8 to 15 years.
The following interventions/exposures will be administered:
Behavioral: Psychological background determinations, Genetic: Genetic susceptibility determination, Procedure/Surgery: Cortisol release test, Procedure/Surgery: Saliva cortisol measurement. Receives: Behavioral: Psychological background determinations; Genetic: Genetic susceptibility determination; Procedure: Cortisol release test; Procedure: Saliva cortisol measurement | |
| Healthy control | Healthy primary school pupils, age from 8 to 15 years.
The following interventions/exposures will be administered:
Behavioral: Psychological background determinations, Genetic: Genetic susceptibility determination, Procedure/Surgery: Saliva cortisol measurement. Receives: Behavioral: Psychological background determinations; Genetic: Genetic susceptibility determination; Procedure: Saliva cortisol measurement |
What is being measured
The primary outcome is the main question the study is designed to answer.
Significant between group differences in metabolic control
Association between psychological scores, stress reactivity, genetic factors and metabolic control in patients with type 1 diabetes
Measured: 1 month
Secondary outcomes (1)
Significant differences in psychological scores between groups
Significant differences in psychological scores between the patients with type 1 diabetes and the control group
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2015 (estimated)
- Study startJul 2015
- Primary completionDec 2019
- Study completionDec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (63)Papers the sponsor has linked to this study.
- Other trials for Type 1 DiabetesStudies 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
- 207 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Ljubljana, Faculty of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tadej Battelino, MD, PhD, Principal investigator, University of Ljubljana, Faculty of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02575001
- Sponsor's protocol ID
- Attachment2015
- Status last verified
- Feb 2020
- First submitted
- 23 Jul 2015
- Last updated
- 11 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
Nolte T, Guiney J, Fonagy P, Mayes LC, Luyten P. Interpersonal stress regulation and the development of anxiety disorders: an attachment-based developmental framework. Front Behav Neurosci. 2011 Sep 21;5:55. doi: 10.3389/fnbeh.2011.00055. eCollection 2011.
PubMed 21960962Lupien SJ, Fiocco A, Wan N, Maheu F, Lord C, Schramek T, Tu MT. Stress hormones and human memory function across the lifespan. Psychoneuroendocrinology. 2005 Apr;30(3):225-42. doi: 10.1016/j.psyneuen.2004.08.003.
PubMed 15511597McEwen BS. Protective and damaging effects of stress mediators. N Engl J Med. 1998 Jan 15;338(3):171-9. doi: 10.1056/NEJM199801153380307. No abstract available.
PubMed 9428819McEwen BS, Biron CA, Brunson KW, Bulloch K, Chambers WH, Dhabhar FS, Goldfarb RH, Kitson RP, Miller AH, Spencer RL, Weiss JM. The role of adrenocorticoids as modulators of immune function in health and disease: neural, endocrine and immune interactions. Brain Res Brain Res Rev. 1997 Feb;23(1-2):79-133. doi: 10.1016/s0165-0173(96)00012-4. No abstract available.
PubMed 9063588Starkman MN, Schteingart DE, Schork MA. Depressed mood and other psychiatric manifestations of Cushing's syndrome: relationship to hormone levels. Psychosom Med. 1981 Feb;43(1):3-18. doi: 10.1097/00006842-198102000-00002.
PubMed 6259680Chu JW, Matthias DF, Belanoff J, Schatzberg A, Hoffman AR, Feldman D. Successful long-term treatment of refractory Cushing's disease with high-dose mifepristone (RU 486). J Clin Endocrinol Metab. 2001 Aug;86(8):3568-73. doi: 10.1210/jcem.86.8.7740.
PubMed 11502780Carrion VG, Weems CF, Ray RD, Glaser B, Hessl D, Reiss AL. Diurnal salivary cortisol in pediatric posttraumatic stress disorder. Biol Psychiatry. 2002 Apr 1;51(7):575-82. doi: 10.1016/s0006-3223(01)01310-5.
PubMed 11950459Feder A, Coplan JD, Goetz RR, Mathew SJ, Pine DS, Dahl RE, Ryan ND, Greenwald S, Weissman MM. Twenty-four-hour cortisol secretion patterns in prepubertal children with anxiety or depressive disorders. Biol Psychiatry. 2004 Aug 1;56(3):198-204. doi: 10.1016/j.biopsych.2004.05.005.
PubMed 15271589Belanoff JK, Kalehzan M, Sund B, Fleming Ficek SK, Schatzberg AF. Cortisol activity and cognitive changes in psychotic major depression. Am J Psychiatry. 2001 Oct;158(10):1612-6. doi: 10.1176/appi.ajp.158.10.1612.
PubMed 11578992Luby JL, Heffelfinger A, Mrakotsky C, Brown K, Hessler M, Spitznagel E. Alterations in stress cortisol reactivity in depressed preschoolers relative to psychiatric and no-disorder comparison groups. Arch Gen Psychiatry. 2003 Dec;60(12):1248-55. doi: 10.1001/archpsyc.60.12.1248.
PubMed 14662557Nemeroff CB. The neurobiology of depression. Sci Am. 1998 Jun;278(6):42-9. doi: 10.1038/scientificamerican0698-42. No abstract available.
PubMed 9608732Matthews SG. Early programming of the hypothalamo-pituitary-adrenal axis. Trends Endocrinol Metab. 2002 Nov;13(9):373-80. doi: 10.1016/s1043-2760(02)00690-2.
PubMed 12367818Oitzl MS, Champagne DL, van der Veen R, de Kloet ER. Brain development under stress: hypotheses of glucocorticoid actions revisited. Neurosci Biobehav Rev. 2010 May;34(6):853-66. doi: 10.1016/j.neubiorev.2009.07.006. Epub 2009 Jul 23.
PubMed 19631685Gunnar MR, Donzella B. Social regulation of the cortisol levels in early human development. Psychoneuroendocrinology. 2002 Jan-Feb;27(1-2):199-220. doi: 10.1016/s0306-4530(01)00045-2.
PubMed 11750779Schore AN. Attachment and the regulation of the right brain. Attach Hum Dev. 2000 Apr;2(1):23-47. doi: 10.1080/146167300361309.
PubMed 11707891
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Influence of Psychobiological Adversity to Children and Adolescents With Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT02575001
- Acronym / sponsor ID
- Attachment2015
- Conditions
- Type 1 Diabetes, Stress
- Keywords
- Type 1 diabetes, Children and adolescents, Stress, Genetic factors, Psychological background
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 207 participants (actual)
- Lead sponsor
- University of Ljubljana, Faculty of MedicineUniversity, hospital or other
- Study start
- Jul 2015 (actual)
- Primary completion
- Dec 2019 (actual)
- Study completion
- Dec 2019 (actual)
- First posted
- 14 Oct 2015 (estimated)
- 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.
The aims of this study are two fold: To show whether there is an increased environmental or genetic susceptibility to stress in patients with T1D and whether it influences diabetes management. And to develop a strategy for the assessment and treatment of patients with T1D and an increased risk for development of psychopathology under stress.
Detailed description
Lately, a marked increase in the incidence and earlier age of onset of type 1 diabetes (T1D) has been noted. These observations could also be connected to an increased prevalence of stressful experiences and a lowered stress tolerance in some children.
The way a person responds to stress is determined by the interplay of genetic and environmental factors. Environmental experiences at specific times of development have been shown to shape individual's hypothalamic-pituitary-adrenal axis (HPA axis) stress response. It is known, that early development of central nervous system is critically dependent on child's interaction with the environment (experience dependent maturation), especially to the attachment to caregivers (most often the mother). Appropriate caregiving is connected to lower basal cortisol levels in children and a more stable HPA axis response after the exposure to stress. Any circumstances that disturbed the formation of the attachment to the primary caregiver (e.g. complications at delivery, psychosocial stressors affecting the mother or mother's postpartum depression) resulted in higher HPA axis responsiveness to stress in the affected children.
Changes in individual genes have also been shown to influence a person's susceptibility to stress and risk for the development of stress-induced psychopathology.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Type 1 diabetes | – | Behavioral: Psychological background determinations, Genetic: Genetic susceptibility determination, Procedure: Cortisol release test, Procedure: Saliva cortisol measurementChildren with Type 1 diabetes, age from 8 to 15 years. The following interventions/exposures will be administered: Behavioral: Psychological background determinations, Genetic: Genetic susceptibility determination, Procedure/Surgery: Cortisol release test, Procedure/Surgery: Saliva cortisol measurement. |
| Healthy control | – | Behavioral: Psychological background determinations, Genetic: Genetic susceptibility determination, Procedure: Saliva cortisol measurementHealthy primary school pupils, age from 8 to 15 years. The following interventions/exposures will be administered: Behavioral: Psychological background determinations, Genetic: Genetic susceptibility determination, Procedure/Surgery: Saliva cortisol measurement. |
Who may qualify
- Ages
- 8 to 15 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- Children of 8 to 15 years of age with type 1 diabetes with their parents; Healthy primary school pupils of 8 to 15 years of age with their parents
Key inclusion criteria (5 listed)
- Informed consent signed by a parent/legal guardian and informed assent signed by the study participant prior study entry
- Diagnosed with Type 1 DM prior to signature of Patient Informed Consent (PIC) (for the T1D group).
- Age between 8-15 years old (inclusive) at signature of PIC
- Treated by the investigator's centre prior signature of PIC (For the T1D group).
- Willing to undergo all study procedures
Key exclusion criteria (2 listed)
- Any documented concomitant chronic disease known to affect diabetes control (e.g. altered renal function, active cancer undergoing treatment, Crohn's disease, ulcerative colitis, Mb Addison disease)
- Any other medical, social or psychological condition that, in the investigator's opinion, makes the patient unable to comply with the study protocol (e.g. intellectual disability).
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 |
|---|---|---|
| Psychological background determinationsFor the psychological background determinations a structured interview and questionnaires will be administered: 1. Child Attachment Interview (CAI) 2. General/sociodemographic questionnaire with the questions on diabetes management, current health status and the child's development in the infancy 3. "Parenting Stress Index" with the "19-item Life Stress Scale" (PSI) 4. Achenbach System of Empirically Based Assessment (CBCL, YSR) 5. Holmes and Rahe "Social readjustment rating scale" 6. Lifetime Incidence of Traumatic Events (LITE) - parent and child reports of child's trauma/loss history (LITE- S/ P) 7. Experiences in Close Relationships - Relationship Structures questionnaire (ECR-RS) | Behavioural | Healthy control, Type 1 diabetes |
| Genetic susceptibility determinationDNA will be isolated from the patients' blood samples and form the control subjects buccal swabs. The genes with expected influence to stress reactivity and mental disorders will be tested. | Genetic | Healthy control, Type 1 diabetes |
| Cortisol release testSynacthen test - will be used with the group of patients with type 1 diabetes to measure HPA axis reactivity | Procedure or surgery | Type 1 diabetes |
| Saliva cortisol measurementSaliva cortisol measurement - will be used with the patients before and after the Synacthen test and with the Hashimoto thyroiditis and the healthy control group before and after the Child Attachment Interview | Procedure or surgery | Healthy control, Type 1 diabetes |
Primary outcome
Significant between group differences in metabolic control
Time frame: 1 month
Association between psychological scores, stress reactivity, genetic factors and metabolic control in patients with type 1 diabetes
1 secondary outcome
Significant differences in psychological scores between groups
Time frame: 1 week
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 11 Feb 2020.
- Background: PubMed 21960962Nolte T, Guiney J, Fonagy P, Mayes LC, Luyten P. Interpersonal stress regulation and the development of anxiety disorders: an attachment-based developmental framework. Front Behav Neurosci. 2011 Sep 21;5:55. doi: 10.3389/fnbeh.2011.00055. eCollection 2011.
- Background: PubMed 15511597Lupien SJ, Fiocco A, Wan N, Maheu F, Lord C, Schramek T, Tu MT. Stress hormones and human memory function across the lifespan. Psychoneuroendocrinology. 2005 Apr;30(3):225-42. doi: 10.1016/j.psyneuen.2004.08.003.
- Background: PubMed 9428819McEwen BS. Protective and damaging effects of stress mediators. N Engl J Med. 1998 Jan 15;338(3):171-9. doi: 10.1056/NEJM199801153380307. No abstract available.
- Background: PubMed 9063588McEwen BS, Biron CA, Brunson KW, Bulloch K, Chambers WH, Dhabhar FS, Goldfarb RH, Kitson RP, Miller AH, Spencer RL, Weiss JM. The role of adrenocorticoids as modulators of immune function in health and disease: neural, endocrine and immune interactions. Brain Res Brain Res Rev. 1997 Feb;23(1-2):79-133. doi: 10.1016/s0165-0173(96)00012-4. No abstract available.
- Background: PubMed 6259680Starkman MN, Schteingart DE, Schork MA. Depressed mood and other psychiatric manifestations of Cushing's syndrome: relationship to hormone levels. Psychosom Med. 1981 Feb;43(1):3-18. doi: 10.1097/00006842-198102000-00002.
- Background: PubMed 11502780Chu JW, Matthias DF, Belanoff J, Schatzberg A, Hoffman AR, Feldman D. Successful long-term treatment of refractory Cushing's disease with high-dose mifepristone (RU 486). J Clin Endocrinol Metab. 2001 Aug;86(8):3568-73. doi: 10.1210/jcem.86.8.7740.
- Background: PubMed 11950459Carrion VG, Weems CF, Ray RD, Glaser B, Hessl D, Reiss AL. Diurnal salivary cortisol in pediatric posttraumatic stress disorder. Biol Psychiatry. 2002 Apr 1;51(7):575-82. doi: 10.1016/s0006-3223(01)01310-5.
- Background: PubMed 15271589Feder A, Coplan JD, Goetz RR, Mathew SJ, Pine DS, Dahl RE, Ryan ND, Greenwald S, Weissman MM. Twenty-four-hour cortisol secretion patterns in prepubertal children with anxiety or depressive disorders. Biol Psychiatry. 2004 Aug 1;56(3):198-204. doi: 10.1016/j.biopsych.2004.05.005.
- Background: PubMed 11578992Belanoff JK, Kalehzan M, Sund B, Fleming Ficek SK, Schatzberg AF. Cortisol activity and cognitive changes in psychotic major depression. Am J Psychiatry. 2001 Oct;158(10):1612-6. doi: 10.1176/appi.ajp.158.10.1612.
- Background: PubMed 14662557Luby JL, Heffelfinger A, Mrakotsky C, Brown K, Hessler M, Spitznagel E. Alterations in stress cortisol reactivity in depressed preschoolers relative to psychiatric and no-disorder comparison groups. Arch Gen Psychiatry. 2003 Dec;60(12):1248-55. doi: 10.1001/archpsyc.60.12.1248.
- Background: PubMed 9608732Nemeroff CB. The neurobiology of depression. Sci Am. 1998 Jun;278(6):42-9. doi: 10.1038/scientificamerican0698-42. No abstract available.
- Background: PubMed 12367818Matthews SG. Early programming of the hypothalamo-pituitary-adrenal axis. Trends Endocrinol Metab. 2002 Nov;13(9):373-80. doi: 10.1016/s1043-2760(02)00690-2.
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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.
Tadej Battelino, MD, PhD principal investigator
University of Ljubljana, Faculty of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Type 1 Diabetes and Stress, run by University of Ljubljana, Faculty of Medicine at 1 site in Slovenia.
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 5 inclusion and 2 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 11 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Slovenia. 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?
Significant between group differences in metabolic control (time frame: 1 month). 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 NCT02575001, which also lists 63 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 11 Feb 2020.