Clinical trial NCT05247840: INTACT Trial - an Observational Study to Assess Neuropathy in Diabetic Children
Official title: INvesTigation the Abnormality of Detrusor ConTractility by Uroflowmetry in Diabetic Children (INTACT Trial) - a Prospective, Cross-sectional, Observational, Controlled Study
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Diabetes Mellitus
Keywords: diabetes
uroflowmetry
neuropathy
paediatric
children
Lead sponsor: Heim Pal Children's Hospital
Sponsor class: OTHER
First posted: 2022-02-21
Enrollment: 350
Sex: ALL
Minimum age (years): 5
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
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.

Brief 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 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.

Eligibility criteria: Inclusion Criteria:

* 5-18 years (boys, girls) with type 1, type 2 and monogenic DM

Exclusion Criteria:

1. Acute febrile condition (≥38 °C core temperature) in the past seven days
2. Acute or chronical urinary tract or kidney disease: renal insufficiency (GFR ≤ 60 mL/min per 1.73 m2, urinary tract infection
3. Urological disease: bladder cancer, urolithiasis, urethral stricture, posterior urethral valve, meatal stenosis, previous genitourinary surgery, conditions causing urinary outflow problems (phimosis, hypospadias, vesicoureteral reflux)
4. Cystic fibrosis-related diabetes (CFRD)
5. Neurological disorders (multiple sclerosis, transient ischaemic attack, transverse myelitis, myelocele, meningomyelocele, previous spinal cord operation, or operation which might injure the sacral nerve plexus)
6. Medicines taken which can cause neuropathy:

   1. Cytostatic agents: cyclophosphamide, platinum-based antineoplastic agents, vinca alkaloids, epothilones, taxanes, proteasome inhibitors, immunomodulatory drugs
   2. Immunosuppressive agents: TNF-alfa inhibitors (adalimumab, infliximab, etanercept), interferon
   3. Cardiovascular medicines: statins, digoxin, amiodaron
   4. Antimicrobial agents: nitrofurantoin, linezolid, voriconazole, itraconazole, antituberculotics, metronidazole, fluoroquinolone
   5. Anti-ulcerative agent: cimetidin
   6. Neuropsychological agents: levodopa, fenitoin
7. Psychiatric disorders that prevents participation / collaboration in the study
8. Constipation (defined according to the Rome IV criteria)
9. Voided volume \<20 mL
10. Patients who are pregnant, or gave birth in the last 12 months
11. Lack of consent of the patient or legal representative; the patient or legal representative withdraws his or her voluntary consent during the study

Primary outcomes:
measure: diagnostic accuracy of uroflowmetry test 1.1
timeFrame: baseline
measure: diagnostic accuracy of uroflowmetry test 1.2
timeFrame: change from baseline at 12 months
measure: diagnostic accuracy of uroflowmetry test 1.3
timeFrame: change from baseline at 24 months
measure: diagnostic accuracy of uroflowmetry test 1.4
timeFrame: change from baseline at 36 months
measure: diagnostic accuracy of uroflowmetry test 1.5
timeFrame: change from baseline at 48 months
measure: diagnostic accuracy of uroflowmetry test 1.6
timeFrame: change from baseline at 60 months
measure: diagnostic accuracy of cardiovascular autonomic dysfunction test 2.1
timeFrame: baseline
measure: diagnostic accuracy of cardiovascular autonomic dysfunction test 2.2
timeFrame: change from baseline at 12 months
measure: diagnostic accuracy of cardiovascular autonomic dysfunction test 2.3
timeFrame: change from baseline at 24 months
measure: diagnostic accuracy of cardiovascular autonomic dysfunction test 2.4
timeFrame: change from baseline at 36 months
measure: diagnostic accuracy of cardiovascular autonomic dysfunction test 2.5
timeFrame: change from baseline at 48 months
measure: diagnostic accuracy of cardiovascular autonomic dysfunction test 2.6
timeFrame: change from baseline at 60 months
measure: diagnostic accuracy of peripheral nerve conduction test 3.1
timeFrame: baseline
measure: diagnostic accuracy of peripheral nerve conduction test 3.2
timeFrame: change from baseline at 12 months
measure: diagnostic accuracy of peripheral nerve conduction test 3.3
timeFrame: change from baseline at 24 months
measure: diagnostic accuracy of peripheral nerve conduction test 3.4
timeFrame: change from baseline at 36 months
measure: diagnostic accuracy of peripheral nerve conduction test 3.5
timeFrame: change from baseline at 48 months
measure: diagnostic accuracy of peripheral nerve conduction test 3.6
timeFrame: change from baseline at 60 months
Secondary outcomes:
measure: metabolic status 1.1
timeFrame: baseline
measure: metabolic status 1.2
timeFrame: change from baseline at 12 months
measure: metabolic status 1.3
timeFrame: change from baseline at 24 months
measure: metabolic status 1.4
timeFrame: change from baseline at 36 months
measure: metabolic status 1.5
timeFrame: change from baseline at 48 months
measure: metabolic status 1.6
timeFrame: change from baseline at 60 months
measure: metabolic status 2.1
timeFrame: baseline
measure: metabolic status 2.2
timeFrame: change from baseline at 12 months
measure: metabolic status 2.3
timeFrame: change from baseline at 24 months
measure: metabolic status 2.4
timeFrame: change from baseline at 36 months
measure: metabolic status 2.5
timeFrame: change from baseline at 48 months
measure: metabolic status 2.6
timeFrame: change from baseline at 60 months
measure: metabolic status 3.1
timeFrame: baseline
measure: metabolic status 3.2
timeFrame: change from baseline at 12 months
measure: metabolic status 3.3
timeFrame: change from baseline at 24 months
measure: metabolic status 3.4
timeFrame: change from baseline at 36 months
measure: metabolic status 3.5
timeFrame: change from baseline at 48 months
measure: metabolic status 3.6
timeFrame: change from baseline at 60 months
measure: metabolic status 4.1
timeFrame: baseline
measure: metabolic status 4.2
timeFrame: change from baseline at 12 months
measure: metabolic status 4.3
timeFrame: change from baseline at 24 months
measure: metabolic status 4.4
timeFrame: change from baseline at 36 months
measure: metabolic status 4.5
timeFrame: change from baseline at 48 months
measure: metabolic status 4.6
timeFrame: change from baseline at 60 months
measure: metabolic status 5.1
timeFrame: baseline
measure: metabolic status 5.2
timeFrame: change from baseline at 12 months
measure: metabolic status 5.3
timeFrame: change from baseline at 24 months
measure: metabolic status 5.4
timeFrame: change from baseline at 36 months
measure: metabolic status 5.5
timeFrame: change from baseline at 48 months
measure: metabolic status 5.6
timeFrame: change from baseline at 60 months
measure: metabolic status 6.1
timeFrame: baseline
measure: metabolic status 6.2
timeFrame: change from baseline at 12 months
measure: metabolic status 6.3
timeFrame: change from baseline at 24 months
measure: metabolic status 6.4
timeFrame: change from baseline at 36 months
measure: metabolic status 6.5
timeFrame: change from baseline at 48 months
measure: metabolic status 6.6
timeFrame: change from baseline at 60 months
measure: metabolic status 7.1
timeFrame: baseline
measure: metabolic status 7.2
timeFrame: change from baseline at 12 months
measure: metabolic status 7.3
timeFrame: change from baseline at 24 months
measure: metabolic status 7.4
timeFrame: change from baseline at 36 months
measure: metabolic status 7.5
timeFrame: change from baseline at 48 months
measure: metabolic status 7.6
timeFrame: change from baseline at 60 months
measure: clinical symptoms of diabetic patients will be measured and compared to healthy children. 8.1
timeFrame: baseline
measure: clinical symptoms of diabetic patients will be measured and compared to healthy children. 8.2
timeFrame: change from baseline at 12 months
measure: clinical symptoms of diabetic patients will be measured and compared to healthy children. 8.3
timeFrame: change from baseline at 24 months
measure: clinical symptoms of diabetic patients will be measured and compared to healthy children. 8.4
timeFrame: change from baseline at 36 months
measure: clinical symptoms of diabetic patients will be measured and compared to healthy children. 8.5
timeFrame: change from baseline at 48 months
measure: clinical symptoms of diabetic patients will be measured and compared to healthy children. 8.6
timeFrame: change from baseline at 60 months
Other outcomes:
Locations:
city: Budapest
country: Hungary
facility: Heim Pal National Pediatric Institute
Study officials:
References:
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