Investigating ambroxol for early dementia with Lewy bodies

A Clinical Trial to Demonstrate Clinical Efficacy on Cognitive, Neuropsychiatric and Functional Outcomes of Ambroxol in New and Early Patients With Prodromal and Mild Dementia With Lewybodies

This study is testing if ambroxol can help people with early dementia with Lewy bodies improve their thinking skills and overall well-being.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 180 (estimated)
• Ages: 50 Years to 85 Years
• Sex: All
• Sponsor: Helse Fonna (Academic / other)
• Locations: 8 sites (Haugesund, Haugesund and 7 other locations)
• Trial ID: NCT04588285 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effects of ambroxol, a glucocerebrosidase enhancing chaperone, on cognitive function, functional decline, and neuropsychiatric symptoms in patients diagnosed with prodromal and early dementia with Lewy bodies (DLB). Participants will be recruited from Norwegian Memory Clinics and randomly assigned to receive either ambroxol or a placebo. The study will last for 18 months, with assessments including cognition, global function, and various biomarkers. Following the blinded phase, all participants will have the opportunity to receive ambroxol for an additional year.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 50 to 85 with a confirmed diagnosis of dementia with Lewy bodies or mild cognitive impairment in DLB.

Not a fit: Patients with severe cognitive impairment or those unable to comply with study procedures may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve cognitive and functional outcomes for patients with early dementia with Lewy bodies.

How similar studies have performed: Other studies have shown promise with similar approaches targeting cognitive decline in dementia, but this specific application of ambroxol is novel.

Eligibility criteria

Inclusion Criteria:

1. Male or female.
2. Age ≥ 50 and ≤ 85 years of age.
3. Confirmed diagnosis of Dementia with Lewy Bodies (DLB) or Mild Cognitive Impairment in DLB (DLB-MCI).
4. MMSE score\>=15
5. Able and willing to provide informed consent prior to any study related assessments and procedures at screening visit 1.
6. Capable of complying with all study procedures.
7. Willing to provide blood samples for genetic analyses of APOE and GBA.
8. Willing and able to self-administer or administer by a caregiver oral ambroxol medication, from day 1 to study end (at 60 mg TID (day 1-7), 120 mg TID (day 8- 14), 315 BID (day 15-21), 315 mg TID (day 22-28) and 420 mg TID (day 29-550)).
9. Able to travel to the participating study site.
10. 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.
11. 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.

Exclusion Criteria:

1. Current treatment with anticoagulants (e.g. warfarin) that might preclude safe completion in the opinion of the Investigator.
2. 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.
3. Exposure to more than three investigational medicinal products within 12 months prior to the first dose in the current study;
4. Confirmed dysphagia that would preclude self-administration of ambroxol up to 6 tablets daily for the duration of day 1 to day 550/Month 18.
5. Significant known lower spinal malformations or other spinal abnormalities that would preclude lumbar puncture.
6. 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.
7. History of known rare hereditary disorders of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
8. History of illegal substance abuse, drug abuse or alcoholism in the opinion of the Investigator that would preclude participation in the study.
9. Donation of blood (one unit or 350 ml) within three months prior to receiving the first dose of the study drug.
10. 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;
11. Any clinically significant or unstable psychiatric, 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:
    1. Impaired renal function
    2. Moderate/Severe hepatic impairment
    3. 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.
    4. Major depression, delirium or psychosis not related to DLB.
    5. Metastatic cancer or terminal illness.
12. Planned major surgery or other major treatments during study period that will interfere with study-obligations.

Where this trial is running

Haugesund, Haugesund and 7 other locations

• Helse Fonna — Haugesund, Haugesund, Norway (Recruiting)
• Haraldsplass Deaconess Hospital — Bergen, Norway (Recruiting)
• University Hospital, Akershus — Hågån, Norway (Recruiting)
• University Hospital, Akershus — Lørenskog, Norway (Recruiting)
• Oslo University Hospital — Oslo, Norway (Recruiting)
• Stavanger University Hospital — Stavanger, Norway (Recruiting)
• University Hospital North-Norway — Tromsø, Norway (Recruiting)
• Trondheim University Hospital — Trondheim, Norway (Recruiting)

Study contacts

• Principal investigator: Arvid Rongve, Phd — [e-mail]
• Study coordinator: Arvid Rongve, Phd

Conditions Dementia With Lewy Bodies; Cognitive; Neuropsychiatric; Functional Outcomes; New and Early Patients; Prodromal; Mild Dementia; Lewybodies