Treatment of Diabetic Neuropathy With Liraglutide

Diabetes Mellitus, Type 1 Clinical Trial

— TODINELI  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02138045
• Other study ID #: TODINELI
• Status: Completed
• Phase: N/A
• Start date: May 2014
• Est. completion date: February 2017

Study information

• Verified date: August 2021
• Source: Aalborg University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: February 2017
• Est. primary completion date: February 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Diabetic Neuropathies
• Type 1 Diabetes Mellitus

Intervention

Drug:
• Placebo treatment
Treatment continues at highest tolereable dose (minimum 1.2 mg/day). Intervention time 26 weeks at target dose.
• Liraglutide treatment
Treatment continues at highest tolereable dose (minimum 1.2 mg/day). Intervention time 26 weeks at target dose.

Locations

Country	Name	City	State
Denmark	Mech-Sense, Department of Medical Gastroenterology, Aalborg University Hospital	Aalborg	Jutland

Sponsors (2)

Lead Sponsor	Collaborator
Aalborg University Hospital	Novo Nordisk A/S

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	HbA1C		After 6 months of treatment with Liraglutide
Other	Biochemical lipid profile		After 6 months of treatment with Liraglutide
Other	Heart rate and blood pressure		After 6 months of treatment with Liraglutide
Other	Weight/body mass index		After 6 months of treatment with Liraglutide
Primary	RIII withdrawal reflex activity (using standard electromyography)		After 6 months of treatment with Liraglutide
Primary	Evoked brain potentials (using standard electroencephalographic brain imaging).		After 6 months of treatment with Liraglutide
Secondary	Heart rate variability/ alterations in simpatico-vagal balance (24 h Holter monitoring)		After 6 months of treatment with Liraglutide
Secondary	Resting brain activity (spectral analysis of resting brain activity)		After 6 months of treatment with Liraglutide
Secondary	Microstructural brain neurodegeneration (assessed by diffuse tensor imaging)		After 6 months of treatment with Liraglutide
Secondary	Variety in day/night blood pressure		After 6 months of treatment with Liraglutide
Secondary	Gut transit assessed by SmartPill (pH, pressure and transit in stomach, small and large intestine)		After 6 months of treatment with Liraglutide
Secondary	Quantitive sensory testing of pressure algometry in muscle		After 6 months of treatment with Liraglutide
Secondary	Capacity of descending pain inhibition induced by a cold pressor test (2C in 120 sec)		After 6 months of treatment with Liraglutide
Secondary	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
Secondary	Metabolic risk factors expressed as adipokines (adiponectin, leptin, resistin) and inflammatory cell markers		After 6 months of treatment with Liraglutide
Secondary	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
Secondary	OCT		After 6 months of treatment with Liraglutide