Treatment of Diabetic Neuropathy With Liraglutide

NCT02138045 | Completed DMC

• 1 other identifier: TODINELI
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Diabetes Mellitus, Type 1; Type 1 Diabetes Mellitus

Keywords

Diabetes Mellitus, Type 1; Diabetic Neuropathy; Liraglutide

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (11)

• 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

Other Outcomes (4)

• HbA1C

  After 6 months of treatment with Liraglutide

• Biochemical lipid profile

  After 6 months of treatment with Liraglutide

• Heart rate and blood pressure

  After 6 months of treatment with Liraglutide

Study Arms (2)

Placebo treatment

PLACEBO COMPARATOR

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

Liraglutide treatment

ACTIVE COMPARATOR

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

Interventions

Placebo treatment DRUG

Treatment continues at highest tolereable dose (minimum 1.2 mg/day). Intervention time 26 weeks at target dose.

Placebo treatment

Liraglutide treatment DRUG

Treatment continues at highest tolereable dose (minimum 1.2 mg/day). Intervention time 26 weeks at target dose.

Liraglutide treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Aalborg University Hospital: lead
• Novo Nordisk A/S: collaborator

Study Sites (1)

Mech-Sense, Department of Medical Gastroenterology, Aalborg University Hospital

Aalborg, Jutland, 9000, Denmark

Location

Related Publications (4)

• Arendt Nielsen T, Sega R, Uggerhoj Andersen C, Vorum H, Drewes AM, Jakobsen PE, Brock B, Brock C. Liraglutide Treatment Does Not Induce Changes in the Peripapillary Retinal Nerve Fiber Layer Thickness in Patients with Diabetic Retinopathy. J Ocul Pharmacol Ther. 2022 Jan-Feb;38(1):114-121. doi: 10.1089/jop.2021.0055. Epub 2021 Dec 16.

  PMID: 34918951 DERIVED

• Nissen TD, Meldgaard T, Nedergaard RW, Juhl AH, Jakobsen PE, Karmisholt J, Drewes AM, Brock B, Brock C. Peripheral, synaptic and central neuronal transmission is affected in type 1 diabetes. J Diabetes Complications. 2020 Sep;34(9):107614. doi: 10.1016/j.jdiacomp.2020.107614. Epub 2020 May 8.

  PMID: 32571684 DERIVED

• Nedergaard RB, Nissen TD, Morch CD, Meldgaard T, Juhl AH, Jakobsen PE, Karmisholt J, Brock B, Drewes AM, Brock C. Diabetic Neuropathy Influences Control of Spinal Mechanisms. J Clin Neurophysiol. 2021 Jul 1;38(4):299-305. doi: 10.1097/WNP.0000000000000691.

  PMID: 32501945 DERIVED

• Brock C, Hansen CS, Karmisholt J, Moller HJ, Juhl A, Farmer AD, Drewes AM, Riahi S, Lervang HH, Jakobsen PE, Brock B. Liraglutide treatment reduced interleukin-6 in adults with type 1 diabetes but did not improve established autonomic or polyneuropathy. Br J Clin Pharmacol. 2019 Nov;85(11):2512-2523. doi: 10.1111/bcp.14063. Epub 2019 Aug 30.

  PMID: 31338868 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetic Neuropathies

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Diabetes Complications

Study Officials

• Asbjørn M. Drewes, Professor

  Mech-Sense, Department of Medical Gastroenterology, Aalborg Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, MD, PhD

Study Record Dates

• First Submitted: May 13, 2014
• First Posted: May 14, 2014
• Study Start: May 1, 2014
• Primary Completion: February 1, 2017
• Study Completion: February 1, 2017
• Last Updated: August 10, 2021

Record last verified: 2021-08

Locations

DK (1)