Ambroxol in Disease Modification in Parkinson Disease (AiM-PD)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02941822|
Recruitment Status : Active, not recruiting
First Posted : October 21, 2016
Last Update Posted : February 22, 2018
|Condition or disease||Intervention/treatment||Phase|
|Parkinson Disease||Drug: Ambroxol||Phase 2|
The AiM-PD study will recruit 20 patients (10 GBA-positive & 10 GBA-negative status) diagnosed with Parkinson disease (PD). Each patient will self-administer the study drug, ambroxol (60 mg per tablet) at 5 intra-dose escalations over the course of 6 months, as shown below:
- Day 1-7: 60 mg three times a day
- Day 8-14: 120 mg three times a day
- Day 15-21: 180 mg three times a day
- Day 22-28: 300 mg three times a day
- Day 29-186: 420 mg three times a day
The study drug is licensed in the EU as an over-the-counter drug to treat respiratory conditions by reducing mucus production. Previous studies have shown that ambroxol can penetrate the brain in rodent and non-human primate models, and may have an effect in slowing PD. The results also indicate individuals who express the GBA mutation (increased risk of PD) are able to reduce the growth of cells that cause PD by stimulating an enzyme called glucocerebrosidase.
The study will collect cerebrospinal fluid, blood, and urine samples before, during and after the drug has been taken over a 6 month period. In these samples the Investigators will measure ambroxol drug levels, assess whether the glucocerebrosidase enzyme has been stimulated and the levels of other substances thought to be associated with the development of PD and confirm whether the study drug has penetrated the cerebrospinal fluid and CNS. The study will administer clinical and cognitive assessments to determine if there is any improvement in patient's PD symptoms. If the study proves ambroxol penetrates the CNS and replicates our current findings in the laboratory, the Investigators shall move on to a much larger drug trial to test whether the study drug may be able to slow the progression of PD.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase IIA Prospective, Single-Centre, Open Label Clinical Trial to Evaluate the Safety, Tolerability and Pharmacodynamic Effects of Ambroxol in Patients With Parkinson Disease: Ambroxol in Disease Modification in Parkinson Disease|
|Study Start Date :||December 2016|
|Estimated Primary Completion Date :||April 2018|
|Estimated Study Completion Date :||April 2018|
Experimental: Arm 1
Each patient will self-administer the study drug, ambroxol (60 mg per tablet) at 5 intra-dose escalations (DE) over the duration of 6 months that will be taken three times a day, see below:
Details outlines in the intervention description.
Other Name: Brand name: Ambrosan
- Glucocerebrosidase and ambroxol levels in blood and cerebrospinal fluid [ Time Frame: Day 1-186 ]Assess ambroxol's central nervous system and cerebrospinal fluid penetration, and its binding to GCase by examining GCase activity & ambroxol levels at 5 intra-participant dose escalations from day 1 to day 186.
- Prevalence of treatment-related adverse events and abnormal investigation findings at each dose escalation level [ Time Frame: Day 1-186 ]
Assess the safety and tolerability of the Glucocerebrosidase (GCase) modulating chaperone ambroxol in Parkinson disease patients with and without Gaucher gene (GBA) mutation at 5 intra-participant dose escalations from day 1 to 186.
This will include:
the number and proportion of subjects with AEs; assessment of clinical laboratory parameters; assessment of vital signs and ECG parameters.
- Pharmacodynamic effects of ambroxol on glucocerebrosidase activity in blood and CSF [ Time Frame: Day 1-186 ]
- Effect of ambroxol on blood and CSF biomarkers [ Time Frame: Day 1-186 ]Quantify the effects of ambroxol on biomarkers of Parkinson and neurodegeneration at 5 intra-participant dose escalations from day 1 to 186.
- Improvement in Montreal Cognitive Assessment (MoCA) and Unified Parkinson's Disease Rating Scale (UPDRS) scores [ Time Frame: Day 1-186 ]
- Improvement in non-motor symptom assessment scale (NMSS) and non-motor symptom questionnaire (NMSQuest) scores. [ Time Frame: Day 1-186 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02941822
|Leonard Wolfson Experimental Neurology Centre Clinical Research Facility LWENC CRF|
|London, United Kingdom|