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Parkinson DiseasePhase 2AiM-PDNCT02941822

Ambroxol in Disease Modification in Parkinson Disease

A Phase 2 study testing Ambroxol in people with Parkinson Disease, run by University College, London at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study will evaluate the safety, tolerability and pharmacodynamics of ambroxol in participants with Parkinson Disease. Participants will administer ambroxol at five dose levels and will undergo clinical assessments, lumbar punctures, venepuncture, biomarker blood analysis and cognitive assessment throughout the… Read more about this study

Who is it for?
Ages 40 to 80 years
Conditions the study is for
Parkinson Disease
What is being tested?
Ambroxol
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
1 siteUnited Kingdom
Study dates
Dec 2016to May 2018
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female;
  • Age ≥ 40 and ≤ 80 years of age;
  • Confirmed diagnosis of Parkinson disease at any time; and Hoehn and Yahr criteria, confirmed staged between I - III, inclusive;
  • Able and willing to provide informed consent prior to any study related assessments and procedures at screening visit 1;
  • Capable of complying with all study procedures, including fasting lumbar puncture;
  • Willing to provide a blood sample for screening genomic for Parkinson Disease related DNA analysis and/or consent to Investigators obtaining and using participants previous DNA results if applicable;
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  • Willing and able to self-administer oral ambroxol medication, from day 1 to 186 (at 60 mg TID (day 1-7), 120 mg TID (day 8-14), 180 mg TID (day 15-21), 300 mg TID (day 22-28) and 420 mg TID (day 29-186));
  • Able to travel to the participating study site;
  • A female participant is eligible to participate if she is of:
  • Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 consecutive months of spontaneous amenorrhea, at least 6 weeks post-surgical bilateral oophorectomy (with or without hysterectomy) or post tubal ligation. In questionable cases, menopausal status will be confirmed by demonstrating levels of follicle stimulating hormone (FSH) 25.8 - 134.8 IU/L and oestradiol < 201 pmol/l at entry.
  • Women of child-bearing potential must use accepted contraceptive methods (listed below), and must have a negative serum at screening visit 1 and urine pregnancy tests at subsequent visits if applicable. An additional pregnancy test will be performed, and results obtained, prior to administration of the first dose of ambroxol.
  • Accepted contraception methods:
  • True abstinence: When this is in line with the preferred and usual lifestyle of the participant. [Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception).
  • Contraceptive Methods with a Failure Rate of < 1%:
  • Oral contraceptive, either combined or progestogen alone;
  • Injectable progestogen;
  • Implants of levonorgestrel;
  • Estrogenic vaginal ring;
  • Percutaneous contraceptive patches;
  • Intrauterine device (IUD) or intrauterine system (IUS) that meets the <1% failure rate as stated in the product label;
  • Please note:
  • All male and female participants of child bearing potential must agree with their partners to use double-barrier birth control or abstinence while participating in the study and for 2 weeks following the last dose of the study drug.
  • Participants may continue to take PD medications including glutamate antagonists, anticholinergics, dopamine agonists, Levodopa (L-DOPA and decarboxylase (DDC) inhibitor), Monoamine oxidase B (MAO-B) inhibitors catechol-O-methyltransferase (COMT) inhibitors, beta blockers, selective serotonin uptake inhibitors (SSRIS), tricyclic antidepressants (TCAs) and indomethacin.

Who cannot join

  • Participants are excluded from participating in this study if 1 or more of the following criteria are met:
  • Current treatment with anticoagulants (e.g. warfarin) that might preclude safe completion of the lumbar puncture and in the opinion of the Investigator;
  • Current use of investigational medicinal product or participation in another interventional clinical trial or who have done so within 30 days prior to the first dose in the current study;
  • Exposure to more than three investigational medicinal products within 12 months prior to the first dose in the current study;
  • Confirmed dysphagia that would preclude self-administration of ambroxol up to 7 tablets TID for the duration of day 1 to day 186);
  • Significant known lower spinal malformations or other spinal abnormalities that would preclude lumbar puncture;
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  • History of known sensitivity to the study medication,ambroxol or its excipients (lactose monohydrate, granulated microcrystalline cellulose, copovidone and magnesium stearate) in the opinion of the investigator that contraindicates their participation;
  • History of known rare hereditary disorders of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption;
  • Evidence or history of hypersensitivity to lidocaine or its derivatives;
  • History of drug abuse or alcoholism in the opinion of the Investigator that would preclude participation in the study;
  • Donation of blood (one unit or 350 ml) within three months prior to receiving the first dose of the study drug;
  • Pregnant or breastfeeding;
  • All participants of child bearing potential in the opinion of the Investigator that would preclude participation in the study and who do not agree to use double-barrier birth control or abstinence while participating in the study and for two weeks following the last dose of study drug;
  • Any clinically significant or unstable medical or surgical condition that in the opinion of the PI or PI-delegated clinician may put the participant at risk when participating in the study or may influence the results of the study or affect the participant's ability to take part in the study, as determined by medical history, physical examinations, electrocardiogram (ECG), or laboratory tests. Such conditions may include:
  • Impaired renal function
  • Moderate/Severe hepatic impairment
  • A major cardiovascular event (e.g. myocardial infarction, acute coronary syndrome, decompensated congestive heart failure, pulmonary embolism, coronary revascularisation that occurred within 6 months prior to the screening visit.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • Leonard Wolfson Experimental Neurology Centre Clinical Research Facility LWENC CRF

    London

Other trials in United Kingdom

About this study

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

This study will evaluate the safety, tolerability and pharmacodynamics of ambroxol in participants with Parkinson Disease. Participants will administer ambroxol at five dose levels and will undergo clinical assessments, lumbar punctures, venepuncture, biomarker blood analysis and cognitive assessment throughout the course of the study.

Read the detailed description

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:

  1. Day 1-7: 60 mg three times a day
  2. Day 8-14: 120 mg three times a day
  3. Day 15-21: 180 mg three times a day
  4. Day 22-28: 300 mg three times a day
  5. 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.

Being tested
Ambroxol
Medical subject headings
Parkinson Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AmbroxolDrug

    Also called Brand name: Ambrosan

    Details outlines in the intervention description.

Study groups in NCT02941822
Study groupRoleWhat they receive
Arm 1ExperimentalEach 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: 1. Day 1-7, 60 mg 2. Day 8-14, 120 mg 3. Day 15-21, 180 mg 4. Day 22-28, 300 mg 5. Day 29-186, 420 mg
Receives: Drug: Ambroxol

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Glucocerebrosidase and ambroxol levels in blood and cerebrospinal fluid

    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.

    Measured: Day 1-186

Secondary outcomes (3)

  1. Prevalence of treatment-related adverse events and abnormal investigation findings at each dose escalation level

    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.

    Measured: Day 1-186

  2. Pharmacodynamic effects of ambroxol on glucocerebrosidase activity in blood and CSF

    Measured: Day 1-186

  3. Effect of ambroxol on blood and CSF biomarkers

    Quantify the effects of ambroxol on biomarkers of Parkinson and neurodegeneration at 5 intra-participant dose escalations from day 1 to 186.

    Measured: Day 1-186

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Oct 2016 (estimated)
  2. Study startDec 2016
  3. Primary completionApr 2018
  4. Study completionMay 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02941822
Sponsor's protocol ID
UCL 15/0118
Acronym
AiM-PD
Status last verified
Apr 2020
First submitted
5 Sep 2016
Last updated
15 Apr 2020
Results posted
No
Data monitoring committee
No
Individual data sharing
Undecided: No, all subject's data will be anonymised.

Publications

  • Mullin S, Smith L, Lee K, D'Souza G, Woodgate P, Elflein J, Hallqvist J, Toffoli M, Streeter A, Hosking J, Heywood WE, Khengar R, Campbell P, Hehir J, Cable S, Mills K, Zetterberg H, Limousin P, Libri V, Foltynie T, Schapira AHV. Ambroxol for the Treatment of Patients With Parkinson Disease With and Without Glucocerebrosidase Gene Mutations: A Nonrandomized, Noncontrolled Trial. JAMA Neurol. 2020 Apr 1;77(4):427-434. doi: 10.1001/jamaneurol.2019.4611.

    PubMed 31930374

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ambroxol in people with Parkinson Disease, run by University College, London at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Glucocerebrosidase and ambroxol levels in blood and cerebrospinal fluid (time frame: Day 1-186). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02941822, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2020.

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