TODINELI Trial A randomized, double-blinded, single-centre, parallel-group, placebo-controlled, prospective trial of the neuroprotective effect of Liraglutide for treatment of diabetic neuropathy in Diabets mellitus type I patients MedDRA version: 17.0 Level: LLT Classification code 10012685 Term: Diabetic polyneuropathy System Organ Class: 100000004852 MedDRA version: 17.0 Level: LLT Classification code 10012682 Term: Diabetic peripheral autonomic neuropathy System Organ Class: 100000004852
Conditions
Interventions
Trade Name: Victoza
Product Name: Victoza
Product Code: Victoza
Pharmaceutical Form: Injection
INN or Proposed INN: LIRAGLUTIDE
CAS Number: 204656-20-2
Concentration unit: mg/ml milligram(s)/millilit
Sponsors
Center of Mech-Sense
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Habile person of Northern European descent 2) Age between 18 to 65 years 3) A verified diagnosis of DM type I for minimum 2 years 4) Stable DM treatment for minimum 3 months prior to screening 5) The participants must be able to read and understand Danish. 6) Peripheral diabetic neuropathy ensured by having abnorm nerve conduction velocity 7) BMI equal to or above 22 8) Personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the trial. 9) Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests and other trial procedures. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) Estimated glomerular filtration rate (s-creatinin/eGFR ) 25) 3) HbA1c level < 7% 4) Patients with any clinically significant laboratory abnormalities, that in the opinion of the investigator may increase the risk associated with trial participation or may interfere with the interpretation of the trial results. 5) Patients on GLP-1 receptor agonist treatment (exenatide, liraglutide or others) or pramlintide or any DPP-4 inhibitor within 3 months prior to screening. 6) Other neurological and/or psychiatric disease 7) Treatment of other endocrinological disease except hypothyreosis 8) Malignant neoplasms requiring chemotherapy, surgery, radiation or palliative care in the previous 5 years. 9) Family or personal history of multiple endocrine neoplasis type 2 (MEN2) or familial medullary thyroid carcinoma 10) Personal history of non-familial medullary thyroid carcinoma 11) Known abuse of alcohol and/or medicine (Alcohol use in accordance with the recommendations by the Danish Health and Medicines Authority are allowed). 12) Known allergy to liraglutide 13) Participation in other clinical trials less than 3 months prior to inclusion 14) Female patients who are pregnant or lactating, or intend to become pregnant and male patients who intend to father a child during the course of the study. 15) In women, a serum pregnancy test will be conducted at baseline based on h-CG in the blood. The investigator will have to ensure that fertile female patients use a safe contraception method during the study and for at least 15 hours after termination of the study medication period. The following methods are considered as safe contraception methods: a. The combined oral contraceptive pill b. Intra uterine device c. Gestagen injection d. Subdermal implantation e. Hormone vaginal ring f. Transdermal plaster
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Alterations in the electrophysiological profile assessed by 1) RIII withdrawal reflex activity (using standard electromyography) and 2) Evoked brain potentials (using standard electroencephalographic brain imaging).;Timepoint(s) of evaluation of this end point: before and after 26 weeks of intervention;Main Objective: Type I Diabetes mellitus The present study is an experimental setup, where we want to explore the neuroprotective effect of liraglutide in controlled and standardized experimental neurophysiological pain models. ;Secondary Objective: In addition, basic pain mechanisms in diabetic neuropathy will be explored as these findings may predict clinical efficacy of liraglutide, based on the patient baseline profile prior to treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Alterations in: 1) Heart rate variability/ alterations in the simpatico-vagal balance; (24 h Holter monitoring) 2) Resting brain activity; (spectral analysis of resting brain activity) 3) Microstructural brain neurodegeneration (assessed by diffuse tensor imaging) 4) Variety in day/night blood pressure; 5) Gut transit assessed by SmartPill; (pH, pressure and transit in stomach, small and large intestine) 6) Quantitive sensory testing of pressure algometry in muscle 7) Capacity of descending pain inhibition induced by a cold pressor test (2°C water in 120 sec) 8) Profile of inflammatory cytokines including IL1ß, TNF-a, IL6, MCP-1 and specific macrophage markers sCD163, sMR, neopterin and HO-1. 9) Alteration of edema in retina;Timepoint(s) of evaluation of this end point: Before and after 26 weeks of intervention | — |
Countries
Denmark
Contacts
Public ContactCenter of Mech-Sense
Aalborg University Hospital
Outcome results
None listed