Exendin-4 as a Treatment for Parkinson's Disease - Pilot Study

University College London (UCL)

Status and phase

Unknown

Phase 2

Conditions

Parkinson's Disease

Treatments

Drug: Exenatide

Study type

Interventional

Funder types

Other

Identifiers

NCT01174810

09/0391

2009-018137-37 (EudraCT Number)

Details and patient eligibility

About

Exenatide is a licensed, safe and effective treatment for patients with Diabetes mellitus. Laboratory work has shown strong, reproducible evidence that this drug has beneficial "disease modifying" effects when given to animals with a range of experimental models of Parkinson's disease (PD). This project aims to make an initial evaluation of possible benefits of Exenatide among patients with moderate symptoms of PD. The drug will be given as a twice daily 10microgram injection under the skin in a similar way to one of the conventional "symptomatic" treatments for PD (Apomorphine).

Forty patients with moderate symptoms of PD will be recruited and randomised to receive Exenatide injections twice daily, or to act as controls in this open label trial. Detailed assessments will be made of all patients at baseline and periodically for a total of 14 months. The primary outcome measure will be the change between baseline and follow up, in the severity of a validated PD assessment scale (the UPDRS part 3 motor score) after an overnight period free of conventional PD medication. Secondary measures will include adverse event reports, self completed questionnaires, and blood test results. Aside from these assessments, all patients will continue their regular PD medications throughout the trial with adjustments made only according to clinical need.

In a subgroup of patients (n=10), brain scans that assess the severity of PD, will be performed at both baseline and follow up to help understand possible mechanisms of action of Exenatide.

Enrollment

40 estimated patients

Sex

All

Ages

45 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Diagnosis of Idiopathic Parkinson's disease of moderate severity- equivalent to Hoehn/ Yahr stage 2 to 2.5 (Bilateral symptoms but still physically independent).

Male or female. Female patients to be post menopausal (defined as 12 months of spontaneous amenorrhoea or 6 months spontaneous amenorrhoea with FSH levels greater than 40mIU/ml), surgically sterilised (post hysterectomy and/or oophorectomy). Male patients with female partners that have child bearing potential must use adequate contraception (condoms +/-spermicidal gel/foam) throughout the duration of the trial period.

Age 45-70 years
Disease onset after age 40 years
Disease duration > 5 years
On L-dopa treatment. Patient must be on oral L-dopa treatment - with or without dopamine agonist including Apomorphine, MAO-B inhibitor, COMT inhibitor, Amantadine, Beta blocker, anticholinergic treatment History of wearing off phenomena- duration of action of single dose of L-dopa < 6 hours Stable PD medication for preceding 3 months- i.e. no change in medication type or dose.
UPDRS motor off medication score >15
L-dopa responsiveness. Defined as >33% improvement in UPDRS motor off medication score following L-dopa challenge
Able to give informed consent
Able to comply with trial protocol and willing to attend necessary clinic visits off medication.

Exclusion criteria

Diagnosis or suspicion of other cause for parkinsonism including Vascular parkinsonism, post traumatic parkinsonism, drug or toxin induced parkinsonism, or other neurodegenerative condition including Multiple System Atrophy, Progressive Supranuclear Palsy, Huntington's disease, Wilson's disease, Pantothenate kinase Neurodegeneration (PKAN), Alzheimer's disease, Creutzfeld Jacob disease.
Known abnormality on CT or MRI brain imaging considered to be causing symptoms or signs of neurological dysfunction, or considered likely to compromise compliance with trial protocol.

Concurrent dementia defined by a score lower than 120 on the Mattis Dementia Rating Scale.

Concurrent severe depression defined by a score greater than 16 on the MADRS Exposure to neuroleptic drugs within 6 months prior to baseline assessment Prior intracerebral surgical intervention for Parkinson's disease including Deep Brain stimulation, lesional surgery, growth factor administration, gene therapy or cell transplant
Already actively participating in a trial of a device, drug or surgical treatment for Parkinson's disease, or trial participation within previous 30 days.
Type 1 Diabetes mellitus
Type 2 Diabetes mellitus on insulin treatment
End stage renal disease or severely impaired renal function with creatinine clearance <30ml/min
History of severe cardiac disease (Angina, Myocardial infarction or cardiac surgery in preceding 2 years)
History of pancreatitis
History of alcoholism
Severe gastrointestinal disease including gastroparesis
Ongoing treatment with sulphonylurea
Females that are pregnant or breast feeding or of child bearing potential.