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

Sponsor
Heim Pal Children's Hospital (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05247840
Collaborator
(none)
350
1
60
5.8

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Diagnostic Test: uroflowmetry
  • Diagnostic Test: Cardiovascular autonomic dysfunction test proposed by Ewing et al.
  • Diagnostic Test: peripheral nerve conduction test

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

Study Type:
Observational
Anticipated Enrollment :
350 participants
Observational Model:
Case-Control
Time Perspective:
Prospective
Official Title:
INvesTigation the Abnormality of Detrusor ConTractility by Uroflowmetry in Diabetic Children (INTACT Trial) - a Prospective, Cross-sectional, Observational, Controlled Study
Anticipated Study Start Date :
Sep 1, 2022
Anticipated Primary Completion Date :
Sep 1, 2023
Anticipated Study Completion Date :
Sep 1, 2027

Arms and Interventions

Arm Intervention/Treatment
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.

Diagnostic Test: uroflowmetry
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.
Other Names:
  • non-invasive urodynamic test
  • Diagnostic Test: 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: peripheral nerve conduction 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.

    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.

    Diagnostic Test: uroflowmetry
    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.
    Other Names:
  • non-invasive urodynamic test
  • Diagnostic Test: 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: peripheral nerve conduction 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.

    Outcome Measures

    Primary Outcome Measures

    1. diagnostic accuracy of uroflowmetry test 1.1 [baseline]

      sensitivity, specificity, positive predictive value, negative predictive value

    2. diagnostic accuracy of uroflowmetry test 1.2 [change from baseline at 12 months]

      sensitivity, specificity, positive predictive value, negative predictive value

    3. diagnostic accuracy of uroflowmetry test 1.3 [change from baseline at 24 months]

      sensitivity, specificity, positive predictive value, negative predictive value

    4. diagnostic accuracy of uroflowmetry test 1.4 [change from baseline at 36 months]

      sensitivity, specificity, positive predictive value, negative predictive value

    5. diagnostic accuracy of uroflowmetry test 1.5 [change from baseline at 48 months]

      sensitivity, specificity, positive predictive value, negative predictive value

    6. diagnostic accuracy of uroflowmetry test 1.6 [change from baseline at 60 months]

      sensitivity, specificity, positive predictive value, negative predictive value

    7. diagnostic accuracy of cardiovascular autonomic dysfunction test 2.1 [baseline]

      sensitivity, specificity, positive predictive value, negative predictive value

    8. diagnostic accuracy of cardiovascular autonomic dysfunction test 2.2 [change from baseline at 12 months]

      sensitivity, specificity, positive predictive value, negative predictive value

    9. diagnostic accuracy of cardiovascular autonomic dysfunction test 2.3 [change from baseline at 24 months]

      sensitivity, specificity, positive predictive value, negative predictive value

    10. diagnostic accuracy of cardiovascular autonomic dysfunction test 2.4 [change from baseline at 36 months]

      sensitivity, specificity, positive predictive value, negative predictive value

    11. diagnostic accuracy of cardiovascular autonomic dysfunction test 2.5 [change from baseline at 48 months]

      sensitivity, specificity, positive predictive value, negative predictive value

    12. diagnostic accuracy of cardiovascular autonomic dysfunction test 2.6 [change from baseline at 60 months]

      sensitivity, specificity, positive predictive value, negative predictive value

    13. diagnostic accuracy of peripheral nerve conduction test 3.1 [baseline]

      sensitivity, specificity, positive predictive value, negative predictive value

    14. diagnostic accuracy of peripheral nerve conduction test 3.2 [change from baseline at 12 months]

      sensitivity, specificity, positive predictive value, negative predictive value

    15. diagnostic accuracy of peripheral nerve conduction test 3.3 [change from baseline at 24 months]

      sensitivity, specificity, positive predictive value, negative predictive value

    16. diagnostic accuracy of peripheral nerve conduction test 3.4 [change from baseline at 36 months]

      sensitivity, specificity, positive predictive value, negative predictive value

    17. diagnostic accuracy of peripheral nerve conduction test 3.5 [change from baseline at 48 months]

      sensitivity, specificity, positive predictive value, negative predictive value

    18. diagnostic accuracy of peripheral nerve conduction test 3.6 [change from baseline at 60 months]

      sensitivity, specificity, positive predictive value, negative predictive value

    Secondary Outcome Measures

    1. metabolic status 1.1 [baseline]

      weight (kg)

    2. metabolic status 1.2 [change from baseline at 12 months]

      weight (kg)

    3. metabolic status 1.3 [change from baseline at 24 months]

      weight (kg)

    4. metabolic status 1.4 [change from baseline at 36 months]

      weight (kg)

    5. metabolic status 1.5 [change from baseline at 48 months]

      weight (kg)

    6. metabolic status 1.6 [change from baseline at 60 months]

      weight (kg)

    7. metabolic status 2.1 [baseline]

      height (cm)

    8. metabolic status 2.2 [change from baseline at 12 months]

      height (cm)

    9. metabolic status 2.3 [change from baseline at 24 months]

      height (cm)

    10. metabolic status 2.4 [change from baseline at 36 months]

      height (cm)

    11. metabolic status 2.5 [change from baseline at 48 months]

      height (cm)

    12. metabolic status 2.6 [change from baseline at 60 months]

      height (cm)

    13. metabolic status 3.1 [baseline]

      body surface (m2 calculated by the Mosteller formula)

    14. metabolic status 3.2 [change from baseline at 12 months]

      body surface (m2 calculated by the Mosteller formula)

    15. metabolic status 3.3 [change from baseline at 24 months]

      body surface (m2 calculated by the Mosteller formula)

    16. metabolic status 3.4 [change from baseline at 36 months]

      body surface (m2 calculated by the Mosteller formula)

    17. metabolic status 3.5 [change from baseline at 48 months]

      body surface (m2 calculated by the Mosteller formula)

    18. metabolic status 3.6 [change from baseline at 60 months]

      body surface (m2 calculated by the Mosteller formula)

    19. metabolic status 4.1 [baseline]

      BMI (kg/m2)

    20. metabolic status 4.2 [change from baseline at 12 months]

      BMI (kg/m2)

    21. metabolic status 4.3 [change from baseline at 24 months]

      BMI (kg/m2)

    22. metabolic status 4.4 [change from baseline at 36 months]

      BMI (kg/m2)

    23. metabolic status 4.5 [change from baseline at 48 months]

      BMI (kg/m2)

    24. metabolic status 4.6 [change from baseline at 60 months]

      BMI (kg/m2)

    25. metabolic status 5.1 [baseline]

      body composition evaluated by the Inbody device

    26. metabolic status 5.2 [change from baseline at 12 months]

      body composition evaluated by the Inbody device

    27. metabolic status 5.3 [change from baseline at 24 months]

      body composition evaluated by the Inbody device

    28. metabolic status 5.4 [change from baseline at 36 months]

      body composition evaluated by the Inbody device

    29. metabolic status 5.5 [change from baseline at 48 months]

      body composition evaluated by the Inbody device

    30. metabolic status 5.6 [change from baseline at 60 months]

      body composition evaluated by the Inbody device

    31. metabolic status 6.1 [baseline]

      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)

    32. metabolic status 6.2 [change from baseline at 12 months]

      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)

    33. metabolic status 6.3 [change from baseline at 24 months]

      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)

    34. metabolic status 6.4 [change from baseline at 36 months]

      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)

    35. metabolic status 6.5 [change from baseline at 48 months]

      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)

    36. metabolic status 6.6 [change from baseline at 60 months]

      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)

    37. metabolic status 7.1 [baseline]

      fluid turnover in 24 hours (mL)

    38. metabolic status 7.2 [change from baseline at 12 months]

      fluid turnover in 24 hours (mL)

    39. metabolic status 7.3 [change from baseline at 24 months]

      fluid turnover in 24 hours (mL)

    40. metabolic status 7.4 [change from baseline at 36 months]

      fluid turnover in 24 hours (mL)

    41. metabolic status 7.5 [change from baseline at 48 months]

      fluid turnover in 24 hours (mL)

    42. metabolic status 7.6 [change from baseline at 60 months]

      fluid turnover in 24 hours (mL)

    43. clinical symptoms of diabetic patients will be measured and compared to healthy children. 8.1 [baseline]

      clinical symptoms (Urgent urination, Daily urine incontinence, Urination during night time, Nocturia, Frequency of bowel movement, Consistency of the stool)

    44. clinical symptoms of diabetic patients will be measured and compared to healthy children. 8.2 [change from baseline at 12 months]

      clinical symptoms (Urgent urination, Daily urine incontinence, Urination during night time, Nocturia, Frequency of bowel movement, Consistency of the stool)

    45. clinical symptoms of diabetic patients will be measured and compared to healthy children. 8.3 [change from baseline at 24 months]

      clinical symptoms (Urgent urination, Daily urine incontinence, Urination during night time, Nocturia, Frequency of bowel movement, Consistency of the stool)

    46. clinical symptoms of diabetic patients will be measured and compared to healthy children. 8.4 [change from baseline at 36 months]

      clinical symptoms (Urgent urination, Daily urine incontinence, Urination during night time, Nocturia, Frequency of bowel movement, Consistency of the stool)

    47. clinical symptoms of diabetic patients will be measured and compared to healthy children. 8.5 [change from baseline at 48 months]

      clinical symptoms (Urgent urination, Daily urine incontinence, Urination during night time, Nocturia, Frequency of bowel movement, Consistency of the stool)

    48. clinical symptoms of diabetic patients will be measured and compared to healthy children. 8.6 [change from baseline at 60 months]

      clinical symptoms (Urgent urination, Daily urine incontinence, Urination during night time, Nocturia, Frequency of bowel movement, Consistency of the stool)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    5 Years to 18 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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:

    7. Cytostatic agents: cyclophosphamide, platinum-based antineoplastic agents, vinca alkaloids, epothilones, taxanes, proteasome inhibitors, immunomodulatory drugs

    8. Immunosuppressive agents: TNF-alfa inhibitors (adalimumab, infliximab, etanercept), interferon

    9. Cardiovascular medicines: statins, digoxin, amiodaron

    10. Antimicrobial agents: nitrofurantoin, linezolid, voriconazole, itraconazole, antituberculotics, metronidazole, fluoroquinolone

    11. Anti-ulcerative agent: cimetidin

    12. Neuropsychological agents: levodopa, fenitoin

    13. Psychiatric disorders that prevents participation / collaboration in the study

    14. Constipation (defined according to the Rome IV criteria)

    15. Voided volume <20 mL

    16. Patients who are pregnant, or gave birth in the last 12 months

    17. Lack of consent of the patient or legal representative; the patient or legal representative withdraws his or her voluntary consent during the study

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Heim Pal National Pediatric Institute Budapest Hungary 1089

    Sponsors and Collaborators

    • Heim Pal Children's Hospital

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    László Szabó MD, PhD, med habil., Prof. Dr. László Szabó M.D., PhD., DSc., Dr., Habil. pediatric nephrologist, urodynamic specialist, Heim Pal Children's Hospital
    ClinicalTrials.gov Identifier:
    NCT05247840
    Other Study ID Numbers:
    • KUT-37/2021
    First Posted:
    Feb 21, 2022
    Last Update Posted:
    Aug 5, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by László Szabó MD, PhD, med habil., Prof. Dr. László Szabó M.D., PhD., DSc., Dr., Habil. pediatric nephrologist, urodynamic specialist, Heim Pal Children's Hospital

    Study Results

    No Results Posted as of Aug 5, 2022