Treatment of Diabetic Neuropathy With Liraglutide

Study Overview
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Brief Summary
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The purpose of this trial is to explore whether liraglutide has a long term effect on clinical symptoms and biomarkers in patients with diabetic neuropathy.

Official Title
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A Randomized, Double-blinded, Single-centre, Parallel-group, Placebo-controlled, Prospective Trial of Neuroprotective Effect of Liraglutide for Treatment of Diabetic Neuropathy.

Conditions
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Diabetes Mellitus, Type 1, Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: Placebo treatment
* Drug: Liraglutide treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Abile person of Northern European descent Age between 18 to 65 years A verified diagnosis of DM type 1 for minimum 2 years (HbA1C=7%) Stable DM treatment (Treatment is considered stable when the patient has been treated with basal-bolus insulin, premixed insulin or continously infused insulin with an insulin dose considered stable by investigator for at least 3 months prior to screening.) The participants must be able to read and understand Danish. Peripheral diabetic neuropathy ensured by having abnormal nerve conduction velocity BMI equal to or above 22 Personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the trial. Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests and other trial procedures. Exclusion Criteria: Diabetes mellitus type II Estimated glomerular filtration rate (s-creatinin/eGRF) < 60 ml/min/1.37m2 Calcitonin > 25 HbA1c level < 7% 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. Patients on GLP-1 receptor agonist treatment (exenatide, liraglutide or others) or pramlintide or any DPP-4 inhibitor within 3 months prior to screening. Other neurological and/or psychiatric disease Treatment of other endocrinological disease except hypothyreosis Malignant neoplasms requiring chemotherapy, surgery, radiation or palliative care in the previous 5 years. Family or personal history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma. Personal history of non-familial medullary thyroid carcinoma Known abuse or alcohol and/or medicine (Alcohol use in accordance with the recommendations by the Danish Health and Medicines Authority are allowed). Known allergy to liraglutide. Participation in other clinical trials less than 3 months prior to inclusion Female patients who are pregnant or lactating, or intend to become pregnant and male patients who intend to father a child during course of the study. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo treatment<br>Placebo solution will be slowly titrated to maximum tolerable dose in order to minimize potential side-effects, hence treatment will follow: First and second week: 0.6 mg/day; Third and fourth week: 1.2 mg/day and Fifth and to sixth week: 1.8 mg/day. | Drug: Placebo treatment<br>* Treatment continues at highest tolereable dose (minimum 1.2 mg/day). Intervention time 26 weeks at target dose.<br>|
| Active Comparator: Liraglutide treatment<br>Liraglutide will be slowly titrated to maximum tolerable dose in order to minimize potential side-effects, hence treatment will follow: First and second week: 0.6 mg/day; Third and fourth week: 1.2 mg/day and Fifth and to sixth week: 1.8 mg/day. | Drug: Liraglutide treatment<br>* Treatment continues at highest tolereable dose (minimum 1.2 mg/day). Intervention time 26 weeks at target dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RIII withdrawal reflex activity (using standard electromyography) |  | After 6 months of treatment with Liraglutide | 
| Evoked brain potentials (using standard electroencephalographic brain imaging). |  | After 6 months of treatment with Liraglutide | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart rate variability/ alterations in simpatico-vagal balance (24 h Holter monitoring) |  | After 6 months of treatment with Liraglutide | 
| Resting brain activity (spectral analysis of resting brain activity) |  | After 6 months of treatment with Liraglutide | 
| Microstructural brain neurodegeneration (assessed by diffuse tensor imaging) |  | After 6 months of treatment with Liraglutide | 
| Variety in day/night blood pressure |  | After 6 months of treatment with Liraglutide | 
| Gut transit assessed by SmartPill (pH, pressure and transit in stomach, small and large intestine) |  | After 6 months of treatment with Liraglutide | 
| Quantitive sensory testing of pressure algometry in muscle |  | After 6 months of treatment with Liraglutide | 
| Capacity of descending pain inhibition induced by a cold pressor test (2C in 120 sec) |  | After 6 months of treatment with Liraglutide | 
| Profile of inflammatory cytokines including IL-beta, TNF-alfa, IL6, MCP-1 and specific markers sCD163, sMR, neopterin and HO-1. |  | After 6 months of treatment with Liraglutide | 
| Metabolic risk factors expressed as adipokines (adiponectin, leptin, resistin) and inflammatory cell markers |  | After 6 months of treatment with Liraglutide | 
| Self assessed symptomatology (Michigan neuropathy screening tool, Quality of life (SF-36), Pain catastrophizing scale (PCS) and self-assessed gastro-intestinal symptoms (PAGI-SYM)) |  | After 6 months of treatment with Liraglutide | 
| OCT |  | After 6 months of treatment with Liraglutide | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus, Type 1, Diabetic Neuropathy, Liraglutide