Effects of Acetyl-DL-Leucine on cerebellar ataxia - a multinational, multicenter, randomized, double-blind, placebo-controlled, 2-way crossover phase III trial
Organizational Data
- DRKS-ID:
- DRKS00009733
- Recruitment Status:
- Recruiting complete, study complete
- Date of registration in DRKS:
- 2016-01-15
- Last update in DRKS:
- 2022-09-29
- Registration type:
- Prospective
Acronym/abbreviation of the study
ALCAT
URL of the study
No Entry
Brief summary in lay language
The overall goal is to evaluate whether Acetyl-DL-Leucine treatment improves clinical ataxia scores, as well as a quality of life, and the two common comorbidities depression and fatigue in participants with cerebellar ataxia. The study aims to describe an efficacy and safety profile for experimental treatment with Acetyl-DL-Leucine compared to placebo intervention. Study participants are patients suffering from cerebellar disease. Up to date, there is no evidence for a therapy for these patients.
Brief summary in scientific language
Cerebellar ataxia is a frequent, mostly chronic, progressive neurodegenerative disorder and a very often-disabling syndrome severely impairing motor functioning and quality of life. Previously, cerebellar ataxia was considered untreatable. Cerebellar disorders are often caused by neurodegenerative diseases of the cerebellum, either hereditary or sporadic diseases. The mean prevalence of cerebellar disease is estimated at about 20 illnesses per 100,000 inhabitants, accordingly there are approximately 15,000 affected patients in Germany alone (www.ataxie.de). All in all, about 50% of the cases are sporadic. Symptoms usually begin in childhood or adolescence and are of progressive nature. Patients with cerebellar ataxia suffer from incoordination of the arms and legs with gait disturbances, vertigo and a tendency to fall and thus significantly reduced mobility, restricted autonomy and social participation. Furthermore, the patients suffer from dysarthria with reduced communication skills. Patients experience lower quality of life than e.g. stroke survivors and costs for the health system and society are higher. This reflects the high socioeconomic burden of the disease. No medication has yet been proven effective for the symptomatic or even causative treatment of degenerative cerebellar ataxia. So far, the only treatment recommendation is physiotherapy and new therapeutic options are urgently needed. The goal of this study is to demonstrate that acetyl-DL-leucine 5 g daily is efficacious in improving motor function and quality of life in patients with cerebellar ataxia offering a good benefit-risk profile. Acetyl-DL-Leucine is an modified essential amino acid. The study is designed as a multicenter, randomized, double-blind, placebo-controlled, 2-way crossover phase III trial. The efficacy of acetyl-DL-leucine is assessed by well-established and easy to apply clinical ataxia scores as well as a questionnaire for quality of life.
Health condition or problem studied
- ICD10:
- G11.0 - Congenital nonprogressive ataxia
- ICD10:
- G11.1 - Early-onset cerebellar ataxia
- ICD10:
- G11.2 - Late-onset cerebellar ataxia
- ICD10:
- G11.8 - Other hereditary ataxias
- ICD10:
- G11.9 - Hereditary ataxia, unspecified
- Healthy volunteers:
- No Entry
Interventions, Observational Groups
- Arm 1:
- Acetyl-DL-Leucine 5 g/day p.o., over a period of 4 weeks after a titration of dosage over a period of 2 weeks. Complete duration of treatment 6 weeks.
- Arm 2:
- Treatment with placebo over a period of 6 weeks
Endpoints
- Primary outcome:
- The primary outcome score is the SARA total score with its absolute changes at the end of each treatment period compared to the period-level baseline defined as SARA score at visit 2 (treatment period 1) and at visit 5 (treatment period 2) Delta (SARAtotal) = SARAtotal (on medication) – SARAtotal (baseline)
- Secondary outcome:
- SCAFI and subscores of SARA, QoL (EQ-5D-5L), depression (BDI-II), fatigue (FSS): absolute changes at the end of the 6-week treatment period compared to the period-level baseline defined as score at visit 2 (treatment period 1) and at visit 5 (treatment period 2). Additionally, change scores at follow-up visit will be assessed. Assessment of safety: Documentation and reporting of side effects (AEs, SAEs, SUSARs)
Study Design
- Purpose:
- Treatment
- Allocation:
- Randomized controlled study
- Control:
-
- Placebo
- Phase:
- III
- Study type:
- Interventional
- Mechanism of allocation concealment:
- No Entry
- Blinding:
- Yes
- Assignment:
- Crossover
- Sequence generation:
- No Entry
- Who is blinded:
-
- Assessor
- Caregiver
- Data analyst
- Investigator/therapist
- Patient/subject
Recruitment
- Recruitment Status:
- Recruiting complete, study complete
- Reason if recruiting stopped or withdrawn:
- No Entry
Recruitment Locations
- Recruitment countries:
-
- Austria
- Germany
- Number of study centers:
- Multicenter study
- Recruitment location(s):
-
- Medical center Department of Neurology, University clinic Tübingen
- Medical center German Center for Neurodegenerative Diseases (DZNE) Center for clinical research/Zentrum für klinische Forschung (ZKF) Bonn
- Medical center Department of Neurology, University clinic Tübingen
- Medical center German Center for Neurodegenerative Diseases (DZNE) Center for clinical research/Zentrum für klinische Forschung (ZKF) Bonn
- Medical center Department of Neurology and Deutsches Schwindel- und Gleichgewichtszentrum (DSGZ) University Hospital Munich, Campus Großhadern München
- Medical center Department of Neurology, University Clinic Essen
- Medical center Department of Neurology, Friedrich-Baur-Institute University Hospital Munich München
- Medical center Department of Neurology Charite Berlin
Recruitment period and number of participants
- Planned study start date:
- 2016-01-18
- Actual study start date:
- 2016-01-25
- Planned study completion date:
- No Entry
- Actual Study Completion Date:
- 2017-07-07
- Target Sample Size:
- 108
- Final Sample Size:
- 108
Inclusion Criteria
- Sex:
- All
- Minimum Age:
- 18 Years
- Maximum Age:
- no maximum age
- Additional Inclusion Criteria:
- Subjects will only be included in the study if they meet all of the following criteria: • Clinically confirmed cerebellar ataxia (CA) with a total SARA-Score ≥ 3 (range 0-40) of hereditary or non-hereditary degenerative type • Patient did not receive any of the following prohibited medication within 4 weeks prior to randomization: o Aminopyridines (including substained-release form) o Acetyl-DL-Leucine o Riluzole o Gabapentin o Varenicline o Chlorzoxazone • The ability to follow study instructions and likely to attend and complete all required visits • Written informed consent of the subject prior to any study specific intervention • Age ≥ 18 years
Exclusion Criteria
Subjects will not be included in the study if any of the following criteria applies: • Subject is not able to give consent • Onset of ataxia in association with stroke, encephalitis, sepsis, hyperthermia or heat stroke • Toxic causes for ataxia of cerebellar type • Rapid progression of ataxia (development of severe ataxia in less than 12 weeks) • Subject suffers from any of the following: o chronic diarrhea o unexplained visual loss o malignancies o insulin-dependent diabetes mellitus • Ataxia due to multiple sclerosis, ischemia, hemorrhage or tumor of the posterior fossa as confirmed by imaging • Ataxia due to clinical likely multisystem atrophy type C (MSA-C) • Diagnosis of clinical likely Friedreich ataxia • Known history of hypersensitivity to the investigational drug or derivates • Liver failure defined as AST/ALT > 300 U/l • Simultaneous participation in another clinical trial or participation in any clinical trial involving administration of an investigational medical product within 30 days prior to the beginning of the clinical trial • Subjects with a physical or psychiatric condition which at the investigator’s discretion may put the subject at risk, may confound the trial results, or may interfere with the subject’s participation in this clinical trial • Known or persistent abuse of medication, drugs or alcohol • Females of childbearing potential, who are not using and not willing to use medically reliable methods of contraception for the entire study duration as listed in the patient informed consent form • Current or planned pregnancy or nursing women • Patients has received any of the following prohibited medication within 4 weeks prior to randomization o Aminopyridines (including substained-release form) o Acetyl-DL-Leucine o Riluzole o Gabapentin o Varenicline o Chlorzoxazone After a wash-out period of at least 4 weeks these patients can be included in the study.
Addresses
Primary Sponsor
- Address:
- Klinikum der Universität München, Campus GroßhadernMarchioninistraße 1581377 MünchenGermany
- Telephone:
- No Entry
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.klinikum.uni-muenchen.de
- Investigator Sponsored/Initiated Trial (IST/IIT):
- Yes
Contact for Scientific Queries
- Address:
- Deutsches Zentrum für Schwindel- und Gleichgewichtsstörungen und Neurologische Klinik und Poliklinik, Campus GroßhadernDr. Katharina FeilMarchioninistrasse 1581377 MünchenGermany
- Telephone:
- 00498944007986
- Fax:
- 004989440078795
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Contact for Public Queries
- Address:
- Deutsches Zentrum für Schwindel- und Gleichgewichtsstörungen und Neurologische Klinik und Poliklinik, Campus GroßhadernDr. med. Katharina FeilMarchioninistrasse 1581377 MünchenGermany
- Telephone:
- 0049/(0)89/4400/76986
- Fax:
- 0049/(0)89/4400/78795
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Sources of Monetary or Material Support
Public funding institutions financed by tax money/Government funding body (German Research Foundation (DFG), Federal Ministry of Education and Research (BMBF), etc.)
- Address:
- Bundesministerium für Bildung und Forschung Dienstsitz BonnHeinemannstr. 253175 BonnGermany
- Telephone:
- No Entry
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.bmbf.de
Ethics Committee
Address Ethics Committee
- Address:
- Ethikkommission der Med. Fakultät der LMUPettenkoferstraße 880336 MünchenGermany
- Telephone:
- +49-89-440055191
- Fax:
- +49-89-440055192
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Vote of leading Ethics Committee
- Vote of leading Ethics Committee
- Date of ethics committee application:
- 2015-09-15
- Ethics committee number:
- 548-15 fed
- Vote of the Ethics Committee:
- Approved
- Date of the vote:
- 2015-11-11
Further identification numbers
- Other primary registry ID:
- No Entry
- EudraCT Number:
- 2015-000460-34
IPD - Individual Participant Data
- Do you plan to make participant-related data (IPD) available to other researchers in an anonymized form?:
- No Entry
- IPD Sharing Plan:
- No Entry
Study protocol and other study documents
- Study protocols:
- No Entry
- Study abstract:
- No Entry
- Other study documents:
- No Entry
- Background literature:
- No Entry
- Related DRKS studies:
- No Entry
Publication of study results
- Planned publication:
- No Entry
- Publikationen/Studienergebnisse:
- Feil K, Adrion C, Boesch S, Doss S, Giordano I, Hengel H, Jacobi H, Klockgether T, Klopstock T, Nachbauer W, Schöls L, Steiner KM, Stendel C, Timmann D, Naumann I, Mansmann U, Strupp M; ALCAT Study Group. Safety and Efficacy of Acetyl-DL-Leucine in Certain Types of Cerebellar Ataxia: The ALCAT Randomized Clinical Crossover Trial. JAMA Netw Open. 2021 Dec 1;4(12):e2135841. doi: 10.1001/jamanetworkopen.2021.35841. PMID: 34905009; PMCID: PMC8672236.
- Date of first publication of study results:
- No Entry
- DRKS entry published for the first time with results:
- No Entry
Basic reporting
- Basic Reporting / Results tables:
- No Entry
- Brief summary of results:
- No Entry