INTACT Trial - an Observational Study to Assess Neuropathy in Diabetic Children

N/ANot Yet RecruitingNCT05247840

Heim Pal Children's Hospital350 enrolled

Overview

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.

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 Type

OBSERVATIONAL

Enrollment

350

Conditions

Diabetes Mellitus

Interventions

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.

Eligibility

Sex: ALLMin age: 5 YearsMax age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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