Exendin-4 as a Treatment for Parkinson's Disease - Pilot Study
Primary Purpose
Parkinson's Disease
Status
Unknown status
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Exenatide
Sponsored by
About this trial
This is an interventional treatment trial for Parkinson's Disease focused on measuring Parkinson's Disease, PD, Moderate Parkinson's Disease
Eligibility Criteria
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.
Sites / Locations
- National Hospital for Neurology and Neurosurgery
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Experimental
Arm Label
Control
Exenatide
Arm Description
Outcomes
Primary Outcome Measures
Change from baseline to 12 months & 14 months between patients on active Exenatide treatment and PD controls in respect of their UPDRS-off-medication motor subscore.
Secondary Outcome Measures
Adverse event profile among patients treated with Exenatide compared with matched PD controls. Change from baseline to 12 months/ 14 months between patients on active treatment and PD controls in respect of list given below
the UPDRS on medication motor subscore
the UPDRS ADL subscore
dyskinesia rating scale
timed motor tests
the Mattis Dementia rating scale
the Montgomery & Asberg Depression rating scale
the PDQ39
the EQ-5D
the NMS Quest
the SCOPA Sleep scale
the SCOPA AUT scale
the Smell Identification test
DAT (SPECT) scan appearances.
Full Information
NCT ID
NCT01174810
First Posted
August 2, 2010
Last Updated
March 22, 2012
Sponsor
University College, London
1. Study Identification
Unique Protocol Identification Number
NCT01174810
Brief Title
Exendin-4 as a Treatment for Parkinson's Disease - Pilot Study
Official Title
An Open Label, Single Site, 12 Month, Phase II, Randomised Controlled Trial Evaluating the Safety and Efficacy of Exendin-4 (Exenatide) in the Treatment of Patients With Moderate Severity Parkinson's Disease.
Study Type
Interventional
2. Study Status
Record Verification Date
March 2012
Overall Recruitment Status
Unknown status
Study Start Date
July 2010 (undefined)
Primary Completion Date
March 2013 (Anticipated)
Study Completion Date
March 2013 (Anticipated)
3. Sponsor/Collaborators
Name of the Sponsor
University College, London
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson's Disease
Keywords
Parkinson's Disease, PD, Moderate Parkinson's Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Control
Arm Type
No Intervention
Arm Title
Exenatide
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Exenatide
Other Intervention Name(s)
Byetta, Exendin-4
Intervention Description
Exenatide, 5 micrograms twice a day for 1 month and 10 micrograms twice a day for 11 months. Total duration of treatment 12 months
Primary Outcome Measure Information:
Title
Change from baseline to 12 months & 14 months between patients on active Exenatide treatment and PD controls in respect of their UPDRS-off-medication motor subscore.
Secondary Outcome Measure Information:
Title
Adverse event profile among patients treated with Exenatide compared with matched PD controls. Change from baseline to 12 months/ 14 months between patients on active treatment and PD controls in respect of list given below
Description
the UPDRS on medication motor subscore
the UPDRS ADL subscore
dyskinesia rating scale
timed motor tests
the Mattis Dementia rating scale
the Montgomery & Asberg Depression rating scale
the PDQ39
the EQ-5D
the NMS Quest
the SCOPA Sleep scale
the SCOPA AUT scale
the Smell Identification test
DAT (SPECT) scan appearances.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
National Hospital for Neurology and Neurosurgery
City
London
ZIP/Postal Code
WC1E 3BG
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
23728174
Citation
Aviles-Olmos I, Dickson J, Kefalopoulou Z, Djamshidian A, Ell P, Soderlund T, Whitton P, Wyse R, Isaacs T, Lees A, Limousin P, Foltynie T. Exenatide and the treatment of patients with Parkinson's disease. J Clin Invest. 2013 Jun;123(6):2730-6. doi: 10.1172/JCI68295.
Results Reference
derived
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Exendin-4 as a Treatment for Parkinson's Disease - Pilot Study
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