Treatment of Diabetic Neuropathy With Liraglutide (TODINELI)

August 9, 2021 updated by: Asbjørn Mohr Drewes, Aalborg University Hospital

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
39

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
    • Jutland
      • Aalborg, Jutland, Denmark, 9000
        • Mech-Sense, Department of Medical Gastroenterology, Aalborg University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
PLACEBO_COMPARATOR: Placebo treatment

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

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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
RIII withdrawal reflex activity (using standard electromyography)
Time Frame: After 6 months of treatment with Liraglutide
After 6 months of treatment with Liraglutide
Evoked brain potentials (using standard electroencephalographic brain imaging).
Time Frame: After 6 months of treatment with Liraglutide
After 6 months of treatment with Liraglutide

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Heart rate variability/ alterations in simpatico-vagal balance (24 h Holter monitoring)
Time Frame: After 6 months of treatment with Liraglutide
After 6 months of treatment with Liraglutide
Resting brain activity (spectral analysis of resting brain activity)
Time Frame: After 6 months of treatment with Liraglutide
After 6 months of treatment with Liraglutide
Microstructural brain neurodegeneration (assessed by diffuse tensor imaging)
Time Frame: After 6 months of treatment with Liraglutide
After 6 months of treatment with Liraglutide
Variety in day/night blood pressure
Time Frame: After 6 months of treatment with Liraglutide
After 6 months of treatment with Liraglutide
Gut transit assessed by SmartPill (pH, pressure and transit in stomach, small and large intestine)
Time Frame: After 6 months of treatment with Liraglutide
After 6 months of treatment with Liraglutide
Quantitive sensory testing of pressure algometry in muscle
Time Frame: After 6 months of treatment with Liraglutide
After 6 months of treatment with Liraglutide
Capacity of descending pain inhibition induced by a cold pressor test (2C in 120 sec)
Time Frame: After 6 months of treatment with Liraglutide
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.
Time Frame: After 6 months of treatment with Liraglutide
After 6 months of treatment with Liraglutide
Metabolic risk factors expressed as adipokines (adiponectin, leptin, resistin) and inflammatory cell markers
Time Frame: After 6 months of treatment with Liraglutide
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))
Time Frame: After 6 months of treatment with Liraglutide
After 6 months of treatment with Liraglutide
OCT
Time Frame: After 6 months of treatment with Liraglutide
After 6 months of treatment with Liraglutide

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Time Frame
HbA1C
Time Frame: After 6 months of treatment with Liraglutide
After 6 months of treatment with Liraglutide
Biochemical lipid profile
Time Frame: After 6 months of treatment with Liraglutide
After 6 months of treatment with Liraglutide
Heart rate and blood pressure
Time Frame: After 6 months of treatment with Liraglutide
After 6 months of treatment with Liraglutide
Weight/body mass index
Time Frame: After 6 months of treatment with Liraglutide
After 6 months of treatment with Liraglutide

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Aalborg University Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Novo Nordisk A/S

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Asbjørn M. Drewes, Professor, Mech-Sense, Department of Medical Gastroenterology, Aalborg Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2014

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2017

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 13, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 13, 2014

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 14, 2014

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 10, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 9, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TODINELI

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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