Current partner codePEPTIDESDE
NCT04305002·Phase 2·INTERVENTIONAL

Exenatide Treatment in Parkinson's Disease

Status

Unknown

Phase

Phase 2

Enrollment

60

Locations

1

Results

Not posted

Publications

0

Study summary

What the protocol is testing.

The development of a disease-modifying therapy that delays, reverses or stops the symptom progression remains the most important unmet goal in the treatment of Parkinson's disease (PD). Apart from its glucose lowering effect, glucagon-like peptide-1 (GLP-1) receptor stimulation has been investigated in animal models of PD and shown to increase neurogenesis, to arrest and possible reverse nigrostriatal damage, and to protect dopaminergic neurons from neurodegeneration. Exenatide is a synthetic analogue of human GLP-1, resistant to the metabolic processes that degrade it in its naturally occurring form. Results from a recent randomised, double-blind, placebo-controlled trial in PD showed that patients in active treatment for one year were improved compared to the placebo arm with regard to their performance in Movement Disorders Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor subscale in the practically defined OFF medication state. The aim of this trial is to investigate the effect of Exenatide, 2 mg, subcutaneous injection, once weekly on disease progression represented by the change in longitudinal Positron emission tomography with 2-deoxy-2-\[fluorine-18\]fluoro- D-glucose (FDG-PET) in individual PD subjects, and to identify an Exenatide-related pattern in FDG-PET that will provide insight into the treatment-effect in the brain. The investigators chose the standard regimen prescribed in Type 2 Diabetes Mellitus (T2DM) and the regimen used in a recent trial in PD. The treatment period will be 18 months, and patients will be randomly assigned to either active treatment or placebo. Patients with PD diagnosis, stable on medication during the last year, and Hoehn and Yahr stage 2 or less will be evaluated for the inclusion.

Interventions

Treatment arms and agents.

DRUG

Exenatide

Injections, 2 mg once weekly for 18 months

DRUG

Placebo

Injections, once weekly for 18 months

Timeline

From registration to results.

  1. First posted

    Mar 12, 2020

  2. Study start

    Jan 21, 2020

  3. Primary completion

    Oct 10, 2023

  4. Study completion

    Oct 10, 2023

  5. Results posted

    Not reported

  6. Registry updated

    Sep 13, 2022

Outcomes

What the study measures.

Primary outcomes

FDG-PET network analysis

Time frame · 21 months

Secondary outcomes

The sum score of MDS-UPDRS part 3 in ON and OFF-medication state

Time frame · 18 and 21 months

MDS-UPDRS part 2

Time frame · 9, 18 and 21 months

MDS-UPDRS part 4

Time frame · 9, 18 and 21 months

Hoehn and Yahr

Time frame · 18 and 21 months

Accelerometer (intensity of physical activity)

Time frame · 18 and 21 months

Accelerometer (steps per day)

Time frame · 18 and 21 months

Accelerometer (time of inactivity per day)

Time frame · 9, 18 and 21 months

Levodopa equivalent daily dose (LEDD)

Time frame · Every 3 months

PDQ-39 mobility subscore

Time frame · 18 months

MDS-UPDRS part 1

Time frame · 18 and 21 months

Non-motor symptom progression

Eligibility

Who can take part.

Minimum age
25 Years
Maximum age
80 Years
Sex
ALL
Healthy volunteers
No

Inclusion Criteria: * Diagnosis of clinically probable Parkinson's disease according to the MDS clinical diagnostic criteria for PD * Males or Females * Hoehn and Yahr stage ≤ 2 in the ON medication state. This implies that all patients will be mobile without assistance during their best "ON" medication periods. * Patients are on levodopa treatment. * No need for extended treatment adjustment, no significant motor fluctuations during the last year. * All patients will be ≥25 and ≤80 years of age * Ability to self-administer, or to arrange carer administration of the trial drug. * Signed informed consent to participate in the trial. Exclusion Criteria: * Atypical or other causes of parkinsonism. Patients with suspected Multiple System Atrophy, Progressive Supranuclear Palsy, drug-induced parkinsonism, vascular parkinsonism, dystonic or essential tremor will not be included in the trial. * Prior intra-cerebral surgical intervention for Parkinson's disease. Patients who have previously undergone Deep Brain Stimulation, intra-cerebral administration of growth factors, gene therapy or cell therapies will not be eligible. * Already actively participating in a trial of a device, drug or surgical treatment for Parkinson's disease. * Previous exposure to Exenatide. * Known abnormality on CT or MRI brain imaging considered likely to compromise compliance with trial protocol/FDG-PET acquisition. * Patients with body mass index below 18.5. Exenatide causes weight loss, and individuals with already low BMI will not be eligible. * Patients with diabetes mellitus type 1. * Patients with prediabetes (HbA1c at screening 42-47 mmol/mol), or T2DM (known diagnosis, ongoing antidiabetic treatment or HbA1c \> 47 mmol-mol and fasting plasma glucose \> 7.0 mmol/L at screening). * History of pancreatitis. Baseline serum amylase value should be within the laboratory normal range +/- 20 percent. * Severe gastrointestinal disease including gastroparesis. * History of alcoholism. * History of severe cardiac disease. * History of pancreas cancer. * History or suspicion of thyroid cancer. Undiagnosed neck lump, hoarse voice, or difficulty swallowing not attributable to PD. * Personal or family history of medullary thyroid cancer. * Patients with Multiple Endocrine Neoplasia 2 (MEN2) syndrome. * End stage renal disease or creatinine clearance \< 50 ml/min. * Hyperlipidaemia. A lipid profile will be tested at the screening visit. Cholesterol or Triglyceride levels greater than 2 x the upper limit of normal will raise suspicion of a familial or acquired hyperlipidaemia and will prompt referral to a relevant specialist for investigation and treatment. * Concurrent treatment with warfarin. * Concurrent severe depression, defined as MADRS score 16. * Concurrent dementia, defined as Mini-Mental State Examination (MMSE) \< 22. * Pregnancy and Breastfeeding. * There are no safety data regarding Exenatide use in pregnancy. Women of childbearing potential should only be included after a confirmed menstrual period and a negative highly sensitive urine or serum pregnancy test, and will be asked at each visit to confirm regular use of an effective method of contraception. Those who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and until the end of the relevant systemic exposure period (i.e. 10 weeks after the last dose of study drug) will not be eligible. The following birth control methods are considered to be acceptable: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomised partner, and sexual abstinence. * Known hypersensitivity or allergy or intolerance to GLP-1. * Known hypersensitivity to Exenatide or any of its excipients. * Potential participants who lack the capacity to give informed consent * Any medical, psychiatric or other condition which in the investigator's opinion compromises the potential participant's ability to participate in the trial.

Study locations

1 registered sites.

Sweden. Showing up to 24 locations stored in the fast local snapshot.

Academic Specialist Center, Center for Neurology, SLSO

Stockholm, Sweden

Publications

Results and literature.

No PMID-linked publications were present in this registry snapshot.

Primary links

Continue at the source.

Related trials

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Put the record in context.

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