Platform Trial to Assess the Efficacy of Multiple Drugs in Amyotrophic Lateral Sclerosis (ALS)

NCT ID: NCT06008249

Last Updated: 2025-06-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

171 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-08-09

Study Completion Date

2026-06-30

Brief Summary

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The objective of this phase III, placebo-controlled platform study is to investigate the efficacy of drugs for patients with ALS (Amyotrophic lateral sclerosis).

Detailed Description

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This study uses an innovative multi-arm, adaptive trial design to investigate the efficacy of multiple treatments simultaneously. Currently one study-arm is active, investigating the efficacy and safety of lithium carbonate versus placebo in patients with ALS. Only patients with a specific UNC13A genotype (approximately 1 in 6 ALS patients) are eligible to participate.

Conditions

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Amyotrophic Lateral Sclerosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Participants will be randomised in a 2:1 ratio to receive either lithium carbonate or placebo
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
Double-blind

Study Groups

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Lithium carbonate

Lithium carbonate 400 mg capsules will be taken once daily, starting with one capsule (400 mg daily) initially titrated up to two or three capsules daily, depending on blood lithium levels. The target range for the lithium plasma level will be between ≥0.4 mmol/l and ≤ 0.8 mmol/l. Maximum duration is 24 months.

Group Type EXPERIMENTAL

Lithium Carbonate 400 MG

Intervention Type DRUG

Lithium carbonate vs placebo (2:1)

Placebo

Patients start with 1 capsule to be taken once daily, with subsequent sham dose adjustments made to patients on placebo to maintain blinding in clinical sites.

Group Type PLACEBO_COMPARATOR

Lithium Carbonate 400 MG

Intervention Type DRUG

Lithium carbonate vs placebo (2:1)

Interventions

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Lithium Carbonate 400 MG

Lithium carbonate vs placebo (2:1)

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. ≥ 18 years at the time of screening.
2. Diagnosis of ALS according to the revised El Escorial criteria (possible, probable-laboratory supported, probable or definite).
3. Capable of providing informed consent and complying with trial procedures, including randomization to sub-studies.
4. TRICALS risk profile \> -6.0 and \< -2.0 \*\*
5. The use of riluzole will be permitted during the study. Subjects taking riluzole must be on a stable dose for at least 30 days prior to the baseline visit, or stopped taking riluzole at least 30 days prior to the baseline visit.
6. Women of childbearing potential\* must have a negative pregnancy test at baseline and be non-lactating.
7. Men must agree to practice contraception for the duration of the trial and for at least 3 months after last dose of study drug.
8. Men must not plan to father a child or to provide sperm for donation for the duration of the trial and 3 months after the last dose of study drug.
9. Women must not be able to become pregnant (e.g. post-menopausal\*\*\*, surgically sterile or using effective birth control methods) for the duration of the study. Effective contraceptives are defined as having a failure rate of less than 1% per year when used consistently and correctly and, when applicable, in accordance with the product label, including: abstinence, hormonal contraception, intrauterine device in place for ≥ 3 months Appendix 1). Women of childbearing potential must have a negative pregnancy test at baseline, and be non-lactating. Women who are pregnant or are actively seeking to become pregnant, and women of reproductive potential who are not using effective contraceptives are excluded.

Exclusion Criteria

1. Laboratory Criteria at baseline:

* ALT (alanine transaminase) ≥ 5 times upper limit of normal (ULN)
* AST (aspartate aminotransferase) ≥ 3 times ULN
* Bilirubin ≥ 1.5 times ULN
* Estimated glomerular filtration rate (eGFR) \< 50 mL / min / 1.73 m2 based on Cystatin C, if not available eGFR can also be calculated based on creatinine clearance.
* Platelet concentration of \< 100 x109 per L
* Absolute neutrophil count of \< 1x109 per L
* Haemoglobin \< 100 g/L (\<6.2 mmol/L)
* Amylase \& lipase ≥ 2 times ULN (suspected pancreatitis)
* Lactate ≥ 2 times ULN (suspected lactate acidosis)
2. Moderate to severe hepatic impairment according to Child-Pugh classification (Class B or higher; score ≥ 7). Child-Pugh classification is based on bilirubin, albumin, International Normalized Ratio (INR) and presence of encephalopathy or ascites.
3. Participation in any other investigational drug trial or using investigational drug (within 30 days prior to screening).
4. Hypothyroidism unresponsive to thyroid hormone supplementation.
5. Subjects using non-invasive ventilation (NIV, ≥22 h per day) or having a tracheostomy.
6. Subjects taking edaravone within 30 days prior to screening. Edaravone is approved by the FDA, but remains an investigational product in Europe and Australia.
7. Clinically significant history of unstable or severe cardiac (e.g. congestive heart failure, coronary insufficiency and arrhythmias), oncological, hepatic or renal disease, neuromuscular diseases, significant pulmonary disorder or other medically significant illness.
8. Drug or alcohol abuse.
9. Unstable psychiatric illness defined as psychosis or untreated major depression within 90 days of the screening visit. This exclusion criterion is based on a prior psychiatric diagnosis that is unstable as determined by the subject's treating Psychiatrist.
10. Presence of frontotemporal dementia which prevents informed consent.


1. Patients heterozygous or homozygous for the A-allele of rs12608932 (UNC13A)
2. Known allergy or hypersensitivity to lithium, or its excipients, or to the components of the placebo.
3. Brain injury with posttraumatic epilepsy or neurologic deficit, excluding a concussion in the medical history. Brain infarction is an exclusion criterion, a transient ischemic attack is not.
4. Addison disease.
5. Patients with the following co-medication: antipsychotics, digoxin and calcium antagonists, carbamazepine, methyldopa, verapamil and diltiazem.
6. Brugada Syndrome or family history of Brugada Syndrome.
7. Plasma sodium \<120 mmol/L
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fight MND

UNKNOWN

Sponsor Role collaborator

Research Foundation Flanders

OTHER

Sponsor Role collaborator

MNDA

UNKNOWN

Sponsor Role collaborator

Thierry Latran Foundation

UNKNOWN

Sponsor Role collaborator

Ulla-Carin Lindquist Foundation

UNKNOWN

Sponsor Role collaborator

Luzon Foundation

UNKNOWN

Sponsor Role collaborator

Alan Davidson Foundation

UNKNOWN

Sponsor Role collaborator

My name'5 Doddie Foundation

UNKNOWN

Sponsor Role collaborator

Stichting ALS Nederland

UNKNOWN

Sponsor Role collaborator

Stichting TRICALS Foundation

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Leonard Van den Berg, MD

Role: STUDY_CHAIR

TRICALS Foundation

Locations

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Flinders Medical Centre

Adelaide, , Australia

Site Status NOT_YET_RECRUITING

Royal Brisbane and Women's Hospital

Brisbane, , Australia

Site Status NOT_YET_RECRUITING

Calvary Health Care Bethlehem

Parkdale, , Australia

Site Status NOT_YET_RECRUITING

Perron Institute

Perth, , Australia

Site Status NOT_YET_RECRUITING

The University of Sydney (Royal prince Alfred hospital)

Sydney, , Australia

Site Status RECRUITING

Concord hospital Sydney

Sydney, , Australia

Site Status NOT_YET_RECRUITING

University Hospital Leuven

Leuven, , Belgium

Site Status RECRUITING

University Medical Center Utrecht

Utrecht, Utrecht, Netherlands

Site Status RECRUITING

Bellvitge University Hospital

Barcelona, , Spain

Site Status RECRUITING

Karolinska University Hospital

Stockholm, , Sweden

Site Status RECRUITING

King's College Hospital

London, , United Kingdom

Site Status RECRUITING

University College London Hospital NHS

London, , United Kingdom

Site Status NOT_YET_RECRUITING

University Hospitals of North Midlands NHS Trust

Stoke-on-Trent, , United Kingdom

Site Status NOT_YET_RECRUITING

Countries

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Australia Belgium Netherlands Spain Sweden United Kingdom

Central Contacts

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Roel Vink, PhD

Role: CONTACT

+31 6 50177777

Leonard van den Berg, MD

Role: CONTACT

0887557939 ext. 0031

Facility Contacts

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Eleanor Ramsey

Role: primary

Eleanor Ramsey

Role: primary

Eleanor Ramsey

Role: primary

Eleanor Ramsey

Role: primary

Eleanor Ramsey

Role: primary

Eleanor Ramsey

Role: primary

Nikita Lamaire

Role: primary

Valerie van Eck

Role: primary

Monica Povedano, MD

Role: primary

Charlotta Molin Edlund

Role: primary

Theresa Chiwera

Role: primary

Andrea Malaspina, MD

Role: primary

Thomas Lambert, MD

Role: primary

Other Identifiers

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MAGNET

Identifier Type: -

Identifier Source: org_study_id

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