Diabetes MellitusINTACTNCT05247840
INTACT Trial - an Observational Study to Assess Neuropathy in Diabetic Children
An observational study of Diabetes Mellitus, run by Heim Pal Children's Hospital at 1 site in Hungary.
Trial summary
It is a prospective, cross-sectional, observational, controlled, single centre clinical study. Diabetic patients fulfilling the inclusion criteria and healthy controls will have uroflowmetry examination, cardiovascular autonomic dysfunction tests (heart rate response to deep breathing, to Valsalva maneuver, blood… Read more about this study
- Who is it for?
- Ages 5 to 18 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus
- What is being tested?
- uroflowmetry, Cardiovascular autonomic dysfunction test proposed by Ewing et al. and peripheral nerve conduction test
- How many people
- 350 participants
- Where
- 1 siteHungary
- Study dates
- 1 Sep 2022to 1 Sep 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 5 to 18 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: Diabetic patients who are treated at the Endocrinology Department and Outpatient Clinic of Heim Pál National Pediatric Institute (HOGYI, Budapest, Hungary) will be enrolled.
Who may be able to join
- 5-18 years (boys, girls) with type 1, type 2 and monogenic DM
Who cannot join
- Acute febrile condition (≥38 °C core temperature) in the past seven days
- Acute or chronical urinary tract or kidney disease: renal insufficiency (GFR ≤ 60 mL/min per 1.73 m2, urinary tract infection
- Urological disease: bladder cancer, urolithiasis, urethral stricture, posterior urethral valve, meatal stenosis, previous genitourinary surgery, conditions causing urinary outflow problems (phimosis, hypospadias, vesicoureteral reflux)
- Cystic fibrosis-related diabetes (CFRD)
- Neurological disorders (multiple sclerosis, transient ischaemic attack, transverse myelitis, myelocele, meningomyelocele, previous spinal cord operation, or operation which might injure the sacral nerve plexus)
- Medicines taken which can cause neuropathy:
Show all 17Show fewer
- Cytostatic agents: cyclophosphamide, platinum-based antineoplastic agents, vinca alkaloids, epothilones, taxanes, proteasome inhibitors, immunomodulatory drugs
- Immunosuppressive agents: TNF-alfa inhibitors (adalimumab, infliximab, etanercept), interferon
- Cardiovascular medicines: statins, digoxin, amiodaron
- Antimicrobial agents: nitrofurantoin, linezolid, voriconazole, itraconazole, antituberculotics, metronidazole, fluoroquinolone
- Anti-ulcerative agent: cimetidin
- Neuropsychological agents: levodopa, fenitoin
- Psychiatric disorders that prevents participation / collaboration in the study
- Constipation (defined according to the Rome IV criteria)
- Voided volume <20 mL
- Patients who are pregnant, or gave birth in the last 12 months
- Lack of consent of the patient or legal representative; the patient or legal representative withdraws his or her voluntary consent during the study
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Martonosi contact
Hungary1 site
Heim Pal National Pediatric Institute
Budapest, 1089
Martonosi, agirmartonosi@gmail.com
László Szabó
About this study
Official title: INvesTigation the Abnormality of Detrusor ConTractility by Uroflowmetry in Diabetic Children (INTACT Trial) - a Prospective, Cross-sectional, Observational, Controlled Study
It is a prospective, cross-sectional, observational, controlled, single centre clinical study. Diabetic patients fulfilling the inclusion criteria and healthy controls will have uroflowmetry examination, cardiovascular autonomic dysfunction tests (heart rate response to deep breathing, to Valsalva maneuver, blood pressure and heart rate response to standing up, and to sustained handgrip), and peripheral nerve conduction test. The primary endpoint is the diagnostic accuracy (sensitivity, specificity, negative and positive predictive values) of the tests. The secondary endpoints are: differences in metabolic status (weight, height, body surface, BMI, laboratory parameters, body composition), fluid turnover, and clinical symptoms of diabetic patients comparing to healthy children.
Read the detailed description
The autonomic nervous system function is examined by the reproducible and standardized cardiovascular reflex tests described by Ewing et al.. During the examination, electrocardiogram and blood pressure values are recorded continuously. Heart rate response to deep inspiration is executed to investigate the parasympathetic nervous system. Peripheral neuropathy is evaluated by nerve conduction test.
The trial will start with a pilot period, when the first 50 diabetic and 50 healthy children will be assessed. This will be followed by a short evaluation period, during which the principal investigators and the study team could make adjustments in the study protocol to ensure feasibility.
- Conditions
- Diabetes Mellitus
- Being tested
- uroflowmetry, Cardiovascular autonomic dysfunction test proposed by Ewing et al., peripheral nerve conduction test
- Keywords
- diabetes, uroflowmetry, neuropathy, paediatric, children
- Medical subject headings
- Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
uroflowmetryDiagnostic test
Also called non-invasive urodynamic test
Uroflowmetry will be performed using a uroflow-cystometer (UroDoc Frytech) which determines Qmax, Qave and TQmax. Voided volume (in mL), voiding time (in sec), average and maximum urinary flow rate (Qave and Qmax in mL/sec), and time to maximum urinary flow (TQmax in sec) will be measured; urine flow acceleration (Qacc in mL/sec2) will be calculated. Qmax and Qave are defined according to the International Children's Continence Society. Voided volume will be measured by the uroflow-cystometer device; boys void in a standing, girls in a sitting position. Postvoid bladder diameter (mm) will be measured by ultrasonography and converted to bladder residual volume (mL). The device will be calibrated according to the prescribed instructions for use by a skilled technician. The examinations will take approximately 10 minutes.
Cardiovascular autonomic dysfunction test proposed by Ewing et al.Diagnostic test
CAD will be assessed by five reproducible and standardized cardiovascular reflex tests described by Ewing et al. Three of the five tests assess parasympathetic function: heart rate response to deep breathing, to standing, and the Valsalva maneuver. Two tests evaluate sympathetic function which are blood pressure responses from lying to standing and at sustained handgrip. Each of these five tests is assigned a score of 0 for normal, 0.5 for borderline, and 1 for abnormal results. The sum of these 5 scores - which is the Ewing score - is used to assess severity of CAD. Patients having Ewing score ≥ 2 form the CAD + group, and patients who have less than 2 form the CAD - group.
peripheral nerve conduction testDiagnostic test
Peripheral neuropathy will be evaluated by nerve conduction test. The device measures motor conduction in the lower extremities. It operates at two dedicated frequencies in order to perform a thick myelin sheath cordless fibre (5Hz) and thin myelinated nerve fibre (2000Hz) examination. The device will be calibrated according to the prescribed instructions for use by a skilled technician.
| Study group | Role | What they receive |
|---|---|---|
| diabetic children | Children aged 5-18 years (boys, girls) with type 1, type 2 and monogenic diabetes mellitus who are treated at the Endocrinology Department and Outpatient Clinic of Heim Pál National Pediatric Institute (HOGYI, Budapest, Hungary) will be enrolled. Definition of diabetes is based on the American Diabetes Association (ADA) criteria. All patients who meet the inclusion criteria will be informed of the possibility of taking part in the INTACT Trial. Receives: Diagnostic Test: uroflowmetry; Diagnostic Test: Cardiovascular autonomic dysfunction test proposed by Ewing et al.; Diagnostic Test: peripheral nerve conduction test | |
| healthy children | Healthy children aged 5-18 years (boys, girls) without any acute or chronical disease will be will enrolled and the same tests will be performed on them as in diabetic children. Children with voided volume <20 mL, postvoid residual volume >15%, and signs of an overstretched bladder [voided volume more than: 30 x age (years) + 30 mL] will be excluded. Receives: Diagnostic Test: uroflowmetry; Diagnostic Test: Cardiovascular autonomic dysfunction test proposed by Ewing et al.; Diagnostic Test: peripheral nerve conduction test |
What is being measured
The primary outcome is the main question the study is designed to answer.
diagnostic accuracy of uroflowmetry test 1.1
sensitivity, specificity, positive predictive value, negative predictive value
Measured: baseline
diagnostic accuracy of uroflowmetry test 1.2
sensitivity, specificity, positive predictive value, negative predictive value
Measured: change from baseline at 12 months
diagnostic accuracy of uroflowmetry test 1.3
sensitivity, specificity, positive predictive value, negative predictive value
Measured: change from baseline at 24 months
diagnostic accuracy of uroflowmetry test 1.4
sensitivity, specificity, positive predictive value, negative predictive value
Measured: change from baseline at 36 months
diagnostic accuracy of uroflowmetry test 1.5
sensitivity, specificity, positive predictive value, negative predictive value
Measured: change from baseline at 48 months
diagnostic accuracy of uroflowmetry test 1.6
sensitivity, specificity, positive predictive value, negative predictive value
Measured: change from baseline at 60 months
diagnostic accuracy of cardiovascular autonomic dysfunction test 2.1
sensitivity, specificity, positive predictive value, negative predictive value
Measured: baseline
diagnostic accuracy of cardiovascular autonomic dysfunction test 2.2
sensitivity, specificity, positive predictive value, negative predictive value
Measured: change from baseline at 12 months
diagnostic accuracy of cardiovascular autonomic dysfunction test 2.3
sensitivity, specificity, positive predictive value, negative predictive value
Measured: change from baseline at 24 months
diagnostic accuracy of cardiovascular autonomic dysfunction test 2.4
sensitivity, specificity, positive predictive value, negative predictive value
Measured: change from baseline at 36 months
diagnostic accuracy of cardiovascular autonomic dysfunction test 2.5
sensitivity, specificity, positive predictive value, negative predictive value
Measured: change from baseline at 48 months
diagnostic accuracy of cardiovascular autonomic dysfunction test 2.6
sensitivity, specificity, positive predictive value, negative predictive value
Measured: change from baseline at 60 months
diagnostic accuracy of peripheral nerve conduction test 3.1
sensitivity, specificity, positive predictive value, negative predictive value
Measured: baseline
diagnostic accuracy of peripheral nerve conduction test 3.2
sensitivity, specificity, positive predictive value, negative predictive value
Measured: change from baseline at 12 months
diagnostic accuracy of peripheral nerve conduction test 3.3
sensitivity, specificity, positive predictive value, negative predictive value
Measured: change from baseline at 24 months
diagnostic accuracy of peripheral nerve conduction test 3.4
sensitivity, specificity, positive predictive value, negative predictive value
Measured: change from baseline at 36 months
diagnostic accuracy of peripheral nerve conduction test 3.5
sensitivity, specificity, positive predictive value, negative predictive value
Measured: change from baseline at 48 months
diagnostic accuracy of peripheral nerve conduction test 3.6
sensitivity, specificity, positive predictive value, negative predictive value
Measured: change from baseline at 60 months
Secondary outcomes (48)
metabolic status 1.1
weight (kg)
Measured: baseline
metabolic status 1.2
weight (kg)
Measured: change from baseline at 12 months
metabolic status 1.3
weight (kg)
Measured: change from baseline at 24 months
metabolic status 1.4
weight (kg)
Measured: change from baseline at 36 months
metabolic status 1.5
weight (kg)
Measured: change from baseline at 48 months
metabolic status 1.6
weight (kg)
Measured: change from baseline at 60 months
metabolic status 2.1
height (cm)
Measured: baseline
metabolic status 2.2
height (cm)
Measured: change from baseline at 12 months
metabolic status 2.3
height (cm)
Measured: change from baseline at 24 months
metabolic status 2.4
height (cm)
Measured: change from baseline at 36 months
metabolic status 2.5
height (cm)
Measured: change from baseline at 48 months
metabolic status 2.6
height (cm)
Measured: change from baseline at 60 months
metabolic status 3.1
body surface (m2 calculated by the Mosteller formula)
Measured: baseline
metabolic status 3.2
body surface (m2 calculated by the Mosteller formula)
Measured: change from baseline at 12 months
metabolic status 3.3
body surface (m2 calculated by the Mosteller formula)
Measured: change from baseline at 24 months
metabolic status 3.4
body surface (m2 calculated by the Mosteller formula)
Measured: change from baseline at 36 months
metabolic status 3.5
body surface (m2 calculated by the Mosteller formula)
Measured: change from baseline at 48 months
metabolic status 3.6
body surface (m2 calculated by the Mosteller formula)
Measured: change from baseline at 60 months
metabolic status 4.1
BMI (kg/m2)
Measured: baseline
metabolic status 4.2
BMI (kg/m2)
Measured: change from baseline at 12 months
metabolic status 4.3
BMI (kg/m2)
Measured: change from baseline at 24 months
metabolic status 4.4
BMI (kg/m2)
Measured: change from baseline at 36 months
metabolic status 4.5
BMI (kg/m2)
Measured: change from baseline at 48 months
metabolic status 4.6
BMI (kg/m2)
Measured: change from baseline at 60 months
metabolic status 5.1
body composition evaluated by the Inbody device
Measured: baseline
metabolic status 5.2
body composition evaluated by the Inbody device
Measured: change from baseline at 12 months
metabolic status 5.3
body composition evaluated by the Inbody device
Measured: change from baseline at 24 months
metabolic status 5.4
body composition evaluated by the Inbody device
Measured: change from baseline at 36 months
metabolic status 5.5
body composition evaluated by the Inbody device
Measured: change from baseline at 48 months
metabolic status 5.6
body composition evaluated by the Inbody device
Measured: change from baseline at 60 months
metabolic status 6.1
laboratory parameters (CRP, ESR, full blood count, Hemoglobin, hematocrit, thrombocyte, glucose, C-peptide, HbA1c, triglyceride, cholesterol, uric acid, creatinine, carbamide, AST, ALT, GGT, LDH, ALP, Na, K, P, Ca, albumin, serum total protein, lipase, amylase, urine rapid test)
Measured: baseline
metabolic status 6.2
laboratory parameters (CRP, ESR, full blood count, Hemoglobin, hematocrit, thrombocyte, glucose, C-peptide, HbA1c, triglyceride, cholesterol, uric acid, creatinine, carbamide, AST, ALT, GGT, LDH, ALP, Na, K, P, Ca, albumin, serum total protein, lipase, amylase, urine rapid test)
Measured: change from baseline at 12 months
metabolic status 6.3
laboratory parameters (CRP, ESR, full blood count, Hemoglobin, hematocrit, thrombocyte, glucose, C-peptide, HbA1c, triglyceride, cholesterol, uric acid, creatinine, carbamide, AST, ALT, GGT, LDH, ALP, Na, K, P, Ca, albumin, serum total protein, lipase, amylase, urine rapid test)
Measured: change from baseline at 24 months
metabolic status 6.4
laboratory parameters (CRP, ESR, full blood count, Hemoglobin, hematocrit, thrombocyte, glucose, C-peptide, HbA1c, triglyceride, cholesterol, uric acid, creatinine, carbamide, AST, ALT, GGT, LDH, ALP, Na, K, P, Ca, albumin, serum total protein, lipase, amylase, urine rapid test)
Measured: change from baseline at 36 months
metabolic status 6.5
laboratory parameters (CRP, ESR, full blood count, Hemoglobin, hematocrit, thrombocyte, glucose, C-peptide, HbA1c, triglyceride, cholesterol, uric acid, creatinine, carbamide, AST, ALT, GGT, LDH, ALP, Na, K, P, Ca, albumin, serum total protein, lipase, amylase, urine rapid test)
Measured: change from baseline at 48 months
metabolic status 6.6
laboratory parameters (CRP, ESR, full blood count, Hemoglobin, hematocrit, thrombocyte, glucose, C-peptide, HbA1c, triglyceride, cholesterol, uric acid, creatinine, carbamide, AST, ALT, GGT, LDH, ALP, Na, K, P, Ca, albumin, serum total protein, lipase, amylase, urine rapid test)
Measured: change from baseline at 60 months
metabolic status 7.1
fluid turnover in 24 hours (mL)
Measured: baseline
metabolic status 7.2
fluid turnover in 24 hours (mL)
Measured: change from baseline at 12 months
metabolic status 7.3
fluid turnover in 24 hours (mL)
Measured: change from baseline at 24 months
metabolic status 7.4
fluid turnover in 24 hours (mL)
Measured: change from baseline at 36 months
metabolic status 7.5
fluid turnover in 24 hours (mL)
Measured: change from baseline at 48 months
metabolic status 7.6
fluid turnover in 24 hours (mL)
Measured: change from baseline at 60 months
clinical symptoms of diabetic patients will be measured and compared to healthy children. 8.1
clinical symptoms (Urgent urination, Daily urine incontinence, Urination during night time, Nocturia, Frequency of bowel movement, Consistency of the stool)
Measured: baseline
clinical symptoms of diabetic patients will be measured and compared to healthy children. 8.2
clinical symptoms (Urgent urination, Daily urine incontinence, Urination during night time, Nocturia, Frequency of bowel movement, Consistency of the stool)
Measured: change from baseline at 12 months
clinical symptoms of diabetic patients will be measured and compared to healthy children. 8.3
clinical symptoms (Urgent urination, Daily urine incontinence, Urination during night time, Nocturia, Frequency of bowel movement, Consistency of the stool)
Measured: change from baseline at 24 months
clinical symptoms of diabetic patients will be measured and compared to healthy children. 8.4
clinical symptoms (Urgent urination, Daily urine incontinence, Urination during night time, Nocturia, Frequency of bowel movement, Consistency of the stool)
Measured: change from baseline at 36 months
clinical symptoms of diabetic patients will be measured and compared to healthy children. 8.5
clinical symptoms (Urgent urination, Daily urine incontinence, Urination during night time, Nocturia, Frequency of bowel movement, Consistency of the stool)
Measured: change from baseline at 48 months
clinical symptoms of diabetic patients will be measured and compared to healthy children. 8.6
clinical symptoms (Urgent urination, Daily urine incontinence, Urination during night time, Nocturia, Frequency of bowel movement, Consistency of the stool)
Measured: change from baseline at 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2022
- Study start1 Sep 2022 (estimated)
- Primary completion1 Sep 2023 (estimated)
- Study completion1 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (17)Papers the sponsor has linked to this study.
- Other trials for Diabetes MellitusStudies 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
- Prospective
- Enrolment
- 350 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Heim Pal Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, László Szabó MD, PhD, med habil., Heim Pal Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05247840
- Sponsor's protocol ID
- KUT-37/2021
- Acronym
- INTACT
- Status last verified
- Aug 2022
- First submitted
- 18 Jan 2022
- Last updated
- 5 Aug 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Petropoulos IN, Ponirakis G, Khan A, Almuhannadi H, Gad H, Malik RA. Diagnosing Diabetic Neuropathy: Something Old, Something New. Diabetes Metab J. 2018 Aug;42(4):255-269. doi: 10.4093/dmj.2018.0056.
PubMed 30136449Yuan Z, Tang Z, He C, Tang W. Diabetic cystopathy: A review. J Diabetes. 2015 Jul;7(4):442-7. doi: 10.1111/1753-0407.12272. Epub 2015 Mar 24.
PubMed 25619174Arrellano-Valdez F, Urrutia-Osorio M, Arroyo C, Soto-Vega E. A comprehensive review of urologic complications in patients with diabetes. Springerplus. 2014 Sep 23;3:549. doi: 10.1186/2193-1801-3-549. eCollection 2014.
PubMed 25332855Fayyad AM, Hill SR, Jones G. Prevalence and risk factors for bothersome lower urinary tract symptoms in women with diabetes mellitus from hospital-based diabetes clinic. Int Urogynecol J Pelvic Floor Dysfunct. 2009 Nov;20(11):1339-44. doi: 10.1007/s00192-009-0949-z. Epub 2009 Jul 15.
PubMed 19603127Kaplan SA, Te AE, Blaivas JG. Urodynamic findings in patients with diabetic cystopathy. J Urol. 1995 Feb;153(2):342-4. doi: 10.1097/00005392-199502000-00013.
PubMed 7815578Agashe S, Petak S. Cardiac Autonomic Neuropathy in Diabetes Mellitus. Methodist Debakey Cardiovasc J. 2018 Oct-Dec;14(4):251-256. doi: 10.14797/mdcj-14-4-251.
PubMed 30788010Ewing DJ, Clarke BF. Autonomic neuropathy: its diagnosis and prognosis. Clin Endocrinol Metab. 1986 Nov;15(4):855-88. doi: 10.1016/s0300-595x(86)80078-0.
PubMed 3536203Barkai L, Szabo L. Urinary bladder dysfunction in diabetic children with and without subclinical cardiovascular autonomic neuropathy. Eur J Pediatr. 1993 Mar;152(3):190-2. doi: 10.1007/BF01956141.
PubMed 8444242Szabo L, Barkai L, Lombay B. Urinary flow disturbance as an early sign of autonomic neuropathy in diabetic children and adolescents. Neurourol Urodyn. 2007;26(2):218-21. doi: 10.1002/nau.20349.
PubMed 17078072Zajaczkowska R, Kocot-Kepska M, Leppert W, Wrzosek A, Mika J, Wordliczek J. Mechanisms of Chemotherapy-Induced Peripheral Neuropathy. Int J Mol Sci. 2019 Mar 22;20(6):1451. doi: 10.3390/ijms20061451.
PubMed 30909387Jones MR, Urits I, Wolf J, Corrigan D, Colburn L, Peterson E, Williamson A, Viswanath O. Drug-Induced Peripheral Neuropathy: A Narrative Review. Curr Clin Pharmacol. 2020;15(1):38-48. doi: 10.2174/1574884714666190121154813.
PubMed 30666914Ewing DJ, Martyn CN, Young RJ, Clarke BF. The value of cardiovascular autonomic function tests: 10 years experience in diabetes. Diabetes Care. 1985 Sep-Oct;8(5):491-8. doi: 10.2337/diacare.8.5.491.
PubMed 4053936Spallone V, Bellavere F, Scionti L, Maule S, Quadri R, Bax G, Melga P, Viviani GL, Esposito K, Morganti R, Cortelli P; Diabetic Neuropathy Study Group of the Italian Society of Diabetology. Recommendations for the use of cardiovascular tests in diagnosing diabetic autonomic neuropathy. Nutr Metab Cardiovasc Dis. 2011 Jan;21(1):69-78. doi: 10.1016/j.numecd.2010.07.005.
PubMed 21247746Lin K, Wei L, Huang Z, Zeng Q. Combination of Ewing test, heart rate variability, and heart rate turbulence analysis for early diagnosis of diabetic cardiac autonomic neuropathy. Medicine (Baltimore). 2017 Nov;96(45):e8296. doi: 10.1097/MD.0000000000008296.
PubMed 29137013Liu G, Li M, Vasanji A, Daneshgari F. Temporal diabetes and diuresis-induced alteration of nerves and vasculature of the urinary bladder in the rat. BJU Int. 2011 Jun;107(12):1988-93. doi: 10.1111/j.1464-410X.2010.09840.x. Epub 2010 Nov 18.
PubMed 21087392
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- INvesTigation the Abnormality of Detrusor ConTractility by Uroflowmetry in Diabetic Children (INTACT Trial) - a Prospective, Cross-sectional, Observational, Controlled Study
- ClinicalTrials.gov ID
- NCT05247840
- Acronym / sponsor ID
- INTACT / KUT-37/2021
- Conditions
- Diabetes Mellitus
- Keywords
- diabetes, uroflowmetry, neuropathy, paediatric, children
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 350 participants (estimated)
- Lead sponsor
- Heim Pal Children's HospitalUniversity, hospital or other
- Study start
- 1 Sep 2022 (estimated)
- Primary completion
- 1 Sep 2023 (estimated)
- Study completion
- 1 Sep 2027 (estimated)
- First posted
- 21 Feb 2022 (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.
It is a prospective, cross-sectional, observational, controlled, single centre clinical study. Diabetic patients fulfilling the inclusion criteria and healthy controls will have uroflowmetry examination, cardiovascular autonomic dysfunction tests (heart rate response to deep breathing, to Valsalva maneuver, blood pressure and heart rate response to standing up, and to sustained handgrip), and peripheral nerve conduction test. The primary endpoint is the diagnostic accuracy (sensitivity, specificity, negative and positive predictive values) of the tests. The secondary endpoints are: differences in metabolic status (weight, height, body surface, BMI, laboratory parameters, body composition), fluid turnover, and clinical symptoms of diabetic patients comparing to healthy children.
Detailed description
The autonomic nervous system function is examined by the reproducible and standardized cardiovascular reflex tests described by Ewing et al.. During the examination, electrocardiogram and blood pressure values are recorded continuously. Heart rate response to deep inspiration is executed to investigate the parasympathetic nervous system. Peripheral neuropathy is evaluated by nerve conduction test.
The trial will start with a pilot period, when the first 50 diabetic and 50 healthy children will be assessed. This will be followed by a short evaluation period, during which the principal investigators and the study team could make adjustments in the study protocol to ensure feasibility.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| diabetic children | – | Diagnostic Test: uroflowmetry, Diagnostic Test: Cardiovascular autonomic dysfunction test proposed by Ewing et al., Diagnostic Test: peripheral nerve conduction testChildren aged 5-18 years (boys, girls) with type 1, type 2 and monogenic diabetes mellitus who are treated at the Endocrinology Department and Outpatient Clinic of Heim Pál National Pediatric Institute (HOGYI, Budapest, Hungary) will be enrolled. Definition of diabetes is based on the American Diabetes Association (ADA) criteria. All patients who meet the inclusion criteria will be informed of the possibility of taking part in the INTACT Trial. |
| healthy children | – | Diagnostic Test: uroflowmetry, Diagnostic Test: Cardiovascular autonomic dysfunction test proposed by Ewing et al., Diagnostic Test: peripheral nerve conduction testHealthy children aged 5-18 years (boys, girls) without any acute or chronical disease will be will enrolled and the same tests will be performed on them as in diabetic children. Children with voided volume <20 mL, postvoid residual volume >15%, and signs of an overstretched bladder [voided volume more than: 30 x age (years) + 30 mL] will be excluded. |
Who may qualify
- Ages
- 5 to 18 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- Diabetic patients who are treated at the Endocrinology Department and Outpatient Clinic of Heim Pál National Pediatric Institute (HOGYI, Budapest, Hungary) will be enrolled.
Key inclusion criteria (1 listed)
- 5-18 years (boys, girls) with type 1, type 2 and monogenic DM
Key exclusion criteria (17 listed)
- Acute febrile condition (≥38 °C core temperature) in the past seven days
- Acute or chronical urinary tract or kidney disease: renal insufficiency (GFR ≤ 60 mL/min per 1.73 m2, urinary tract infection
- Urological disease: bladder cancer, urolithiasis, urethral stricture, posterior urethral valve, meatal stenosis, previous genitourinary surgery, conditions causing urinary outflow problems (phimosis, hypospadias, vesicoureteral reflux)
- Cystic fibrosis-related diabetes (CFRD)
- Neurological disorders (multiple sclerosis, transient ischaemic attack, transverse myelitis, myelocele, meningomyelocele, previous spinal cord operation, or operation which might injure the sacral nerve plexus)
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 |
|---|---|---|
| uroflowmetryAlso: non-invasive urodynamic testUroflowmetry will be performed using a uroflow-cystometer (UroDoc Frytech) which determines Qmax, Qave and TQmax. Voided volume (in mL), voiding time (in sec), average and maximum urinary flow rate (Qave and Qmax in mL/sec), and time to maximum urinary flow (TQmax in sec) will be measured; urine flow acceleration (Qacc in mL/sec2) will be calculated. Qmax and Qave are defined according to the International Children's Continence Society. Voided volume will be measured by the uroflow-cystometer device; boys void in a standing, girls in a sitting position. Postvoid bladder diameter (mm) will be measured by ultrasonography and converted to bladder residual volume (mL). The device will be calibrated according to the prescribed instructions for use by a skilled technician. The examinations will take approximately 10 minutes. | Diagnostic test | diabetic children, healthy children |
| Cardiovascular autonomic dysfunction test proposed by Ewing et al.CAD will be assessed by five reproducible and standardized cardiovascular reflex tests described by Ewing et al. Three of the five tests assess parasympathetic function: heart rate response to deep breathing, to standing, and the Valsalva maneuver. Two tests evaluate sympathetic function which are blood pressure responses from lying to standing and at sustained handgrip. Each of these five tests is assigned a score of 0 for normal, 0.5 for borderline, and 1 for abnormal results. The sum of these 5 scores - which is the Ewing score - is used to assess severity of CAD. Patients having Ewing score ≥ 2 form the CAD + group, and patients who have less than 2 form the CAD - group. | Diagnostic test | diabetic children, healthy children |
| peripheral nerve conduction testPeripheral neuropathy will be evaluated by nerve conduction test. The device measures motor conduction in the lower extremities. It operates at two dedicated frequencies in order to perform a thick myelin sheath cordless fibre (5Hz) and thin myelinated nerve fibre (2000Hz) examination. The device will be calibrated according to the prescribed instructions for use by a skilled technician. | Diagnostic test | diabetic children, healthy children |
Primary outcome
diagnostic accuracy of uroflowmetry test 1.1
Time frame: baseline
sensitivity, specificity, positive predictive value, negative predictive value
diagnostic accuracy of uroflowmetry test 1.2
Time frame: change from baseline at 12 months
sensitivity, specificity, positive predictive value, negative predictive value
diagnostic accuracy of uroflowmetry test 1.3
Time frame: change from baseline at 24 months
sensitivity, specificity, positive predictive value, negative predictive value
diagnostic accuracy of uroflowmetry test 1.4
Time frame: change from baseline at 36 months
sensitivity, specificity, positive predictive value, negative predictive value
diagnostic accuracy of uroflowmetry test 1.5
Time frame: change from baseline at 48 months
sensitivity, specificity, positive predictive value, negative predictive value
diagnostic accuracy of uroflowmetry test 1.6
Time frame: change from baseline at 60 months
sensitivity, specificity, positive predictive value, negative predictive value
diagnostic accuracy of cardiovascular autonomic dysfunction test 2.1
Time frame: baseline
sensitivity, specificity, positive predictive value, negative predictive value
diagnostic accuracy of cardiovascular autonomic dysfunction test 2.2
Time frame: change from baseline at 12 months
sensitivity, specificity, positive predictive value, negative predictive value
diagnostic accuracy of cardiovascular autonomic dysfunction test 2.3
Time frame: change from baseline at 24 months
sensitivity, specificity, positive predictive value, negative predictive value
diagnostic accuracy of cardiovascular autonomic dysfunction test 2.4
Time frame: change from baseline at 36 months
sensitivity, specificity, positive predictive value, negative predictive value
diagnostic accuracy of cardiovascular autonomic dysfunction test 2.5
Time frame: change from baseline at 48 months
sensitivity, specificity, positive predictive value, negative predictive value
diagnostic accuracy of cardiovascular autonomic dysfunction test 2.6
Time frame: change from baseline at 60 months
sensitivity, specificity, positive predictive value, negative predictive value
diagnostic accuracy of peripheral nerve conduction test 3.1
Time frame: baseline
sensitivity, specificity, positive predictive value, negative predictive value
diagnostic accuracy of peripheral nerve conduction test 3.2
Time frame: change from baseline at 12 months
sensitivity, specificity, positive predictive value, negative predictive value
diagnostic accuracy of peripheral nerve conduction test 3.3
Time frame: change from baseline at 24 months
sensitivity, specificity, positive predictive value, negative predictive value
diagnostic accuracy of peripheral nerve conduction test 3.4
Time frame: change from baseline at 36 months
sensitivity, specificity, positive predictive value, negative predictive value
diagnostic accuracy of peripheral nerve conduction test 3.5
Time frame: change from baseline at 48 months
sensitivity, specificity, positive predictive value, negative predictive value
diagnostic accuracy of peripheral nerve conduction test 3.6
Time frame: change from baseline at 60 months
sensitivity, specificity, positive predictive value, negative predictive value
48 secondary outcomes
metabolic status 1.1
Time frame: baseline
metabolic status 1.2
Time frame: change from baseline at 12 months
metabolic status 1.3
Time frame: change from baseline at 24 months
metabolic status 1.4
Time frame: change from baseline at 36 months
metabolic status 1.5
Time frame: change from baseline at 48 months
metabolic status 1.6
Time frame: change from baseline at 60 months
metabolic status 2.1
Time frame: baseline
metabolic status 2.2
Time frame: change from baseline at 12 months
metabolic status 2.3
Time frame: change from baseline at 24 months
metabolic status 2.4
Time frame: change from baseline at 36 months
metabolic status 2.5
Time frame: change from baseline at 48 months
metabolic status 2.6
Time frame: change from baseline at 60 months
metabolic status 3.1
Time frame: baseline
metabolic status 3.2
Time frame: change from baseline at 12 months
metabolic status 3.3
Time frame: change from baseline at 24 months
metabolic status 3.4
Time frame: change from baseline at 36 months
metabolic status 3.5
Time frame: change from baseline at 48 months
metabolic status 3.6
Time frame: change from baseline at 60 months
metabolic status 4.1
Time frame: baseline
metabolic status 4.2
Time frame: change from baseline at 12 months
metabolic status 4.3
Time frame: change from baseline at 24 months
metabolic status 4.4
Time frame: change from baseline at 36 months
metabolic status 4.5
Time frame: change from baseline at 48 months
metabolic status 4.6
Time frame: change from baseline at 60 months
metabolic status 5.1
Time frame: baseline
metabolic status 5.2
Time frame: change from baseline at 12 months
metabolic status 5.3
Time frame: change from baseline at 24 months
metabolic status 5.4
Time frame: change from baseline at 36 months
metabolic status 5.5
Time frame: change from baseline at 48 months
metabolic status 5.6
Time frame: change from baseline at 60 months
metabolic status 6.1
Time frame: baseline
metabolic status 6.2
Time frame: change from baseline at 12 months
metabolic status 6.3
Time frame: change from baseline at 24 months
metabolic status 6.4
Time frame: change from baseline at 36 months
metabolic status 6.5
Time frame: change from baseline at 48 months
metabolic status 6.6
Time frame: change from baseline at 60 months
metabolic status 7.1
Time frame: baseline
metabolic status 7.2
Time frame: change from baseline at 12 months
metabolic status 7.3
Time frame: change from baseline at 24 months
metabolic status 7.4
Time frame: change from baseline at 36 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2022.
- Background: PubMed 30136449Petropoulos IN, Ponirakis G, Khan A, Almuhannadi H, Gad H, Malik RA. Diagnosing Diabetic Neuropathy: Something Old, Something New. Diabetes Metab J. 2018 Aug;42(4):255-269. doi: 10.4093/dmj.2018.0056.
- Background: PubMed 25619174Yuan Z, Tang Z, He C, Tang W. Diabetic cystopathy: A review. J Diabetes. 2015 Jul;7(4):442-7. doi: 10.1111/1753-0407.12272. Epub 2015 Mar 24.
- Background: PubMed 25332855Arrellano-Valdez F, Urrutia-Osorio M, Arroyo C, Soto-Vega E. A comprehensive review of urologic complications in patients with diabetes. Springerplus. 2014 Sep 23;3:549. doi: 10.1186/2193-1801-3-549. eCollection 2014.
- Background: PubMed 19603127Fayyad AM, Hill SR, Jones G. Prevalence and risk factors for bothersome lower urinary tract symptoms in women with diabetes mellitus from hospital-based diabetes clinic. Int Urogynecol J Pelvic Floor Dysfunct. 2009 Nov;20(11):1339-44. doi: 10.1007/s00192-009-0949-z. Epub 2009 Jul 15.
- Background: PubMed 7815578Kaplan SA, Te AE, Blaivas JG. Urodynamic findings in patients with diabetic cystopathy. J Urol. 1995 Feb;153(2):342-4. doi: 10.1097/00005392-199502000-00013.
- Background: PubMed 30788010Agashe S, Petak S. Cardiac Autonomic Neuropathy in Diabetes Mellitus. Methodist Debakey Cardiovasc J. 2018 Oct-Dec;14(4):251-256. doi: 10.14797/mdcj-14-4-251.
- Background: PubMed 3536203Ewing DJ, Clarke BF. Autonomic neuropathy: its diagnosis and prognosis. Clin Endocrinol Metab. 1986 Nov;15(4):855-88. doi: 10.1016/s0300-595x(86)80078-0.
- Background: PubMed 8444242Barkai L, Szabo L. Urinary bladder dysfunction in diabetic children with and without subclinical cardiovascular autonomic neuropathy. Eur J Pediatr. 1993 Mar;152(3):190-2. doi: 10.1007/BF01956141.
- Background: PubMed 17078072Szabo L, Barkai L, Lombay B. Urinary flow disturbance as an early sign of autonomic neuropathy in diabetic children and adolescents. Neurourol Urodyn. 2007;26(2):218-21. doi: 10.1002/nau.20349.
- Background: PubMed 30909387Zajaczkowska R, Kocot-Kepska M, Leppert W, Wrzosek A, Mika J, Wordliczek J. Mechanisms of Chemotherapy-Induced Peripheral Neuropathy. Int J Mol Sci. 2019 Mar 22;20(6):1451. doi: 10.3390/ijms20061451.
- Background: PubMed 30666914Jones MR, Urits I, Wolf J, Corrigan D, Colburn L, Peterson E, Williamson A, Viswanath O. Drug-Induced Peripheral Neuropathy: A Narrative Review. Curr Clin Pharmacol. 2020;15(1):38-48. doi: 10.2174/1574884714666190121154813.
- Background: PubMed 4053936Ewing DJ, Martyn CN, Young RJ, Clarke BF. The value of cardiovascular autonomic function tests: 10 years experience in diabetes. Diabetes Care. 1985 Sep-Oct;8(5):491-8. doi: 10.2337/diacare.8.5.491.
- Individual participant dataSharing planned: Undecided
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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.
Martonosi contact
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 Diabetes Mellitus, run by Heim Pal Children's Hospital at 1 site in Hungary.
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 1 inclusion and 17 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: opening soon, as of the sponsor's last update on 5 Aug 2022. 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 Hungary. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Szabó (0614599100 ext. 1155, szabo.laszlo.md@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
diagnostic accuracy of uroflowmetry test 1.1 (time frame: baseline). The study lists 18 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 NCT05247840, which also lists 17 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 5 Aug 2022.