Efficacy and Tolerability of Tauroursodeoxycholic Acid in Amyotrophic Lateral Sclerosis

NCT00877604 | Completed Phase 2 Results DMC

• 2 other identifiers: TUDCA200701EudraCT No.: 2007-001592-10
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

The preclinical rationale for tauroursodeoxycholic acid (TUDCA) use in treating patients with amyotrophic lateral sclerosis (ALS) stems from the demonstration of antioxidant, antiapoptotic and neuroprotective properties of TUDCA in the central nervous system (CNS), both in vitro and in vivo models. This protocol is meant for assessing if the addition of TUDCA to the conventional therapy can improve the therapeutic outcome in patients affected by ALS. Safety will be assessed for all subjects, for the entire duration of the study. 30 patients affected by ALS with site of onset in the limbs will be recruited. All enrolled subjects will continue receiving riluzole at the same regimen as before entering the trial. Based on an appropriate random code, subjects will be divided into two groups of equal size treated, after a lead-in period of 3 months, by oral route with TUDCA at the dose 2 g daily for 1 year or with identical placebo by oral route at the same dosing schedule, under double-blind conditions. Every concomitant and/or supportive therapy will be admitted. Evaluation criteria: Efficacy. The proportion of responder patients in the two treatment groups was the primary outcome measure of the study. Responder patients were defined as those subjects showing an improvement of at least 15% in the ALSFRS-R (2) slope during the treatment period as compared to the lead-in period. This threshold was chosen based according to the consensus conference on designing and implementing clinical trials in ALS (3). Other parameters will include ALSFRS-R at study end, FVC%, the SF-36 quality of life rating scale, time to tracheotomy from starting of study medication dosing (if appropriate), survival Time from starting of study medication dosing (if appropriate), Medical Research Council scores for right and left muscle groups. Safety. Incidence, severity and type of adverse events; changes in clinical laboratory findings.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

ALS; Therapy; Tauroursodeoxycholic acid; TUDCA; antioxidant; antiapoptotic drug; neuroprotective drug

Outcome Measures

Primary Outcomes (1)

• The Proportion of Responder Patients in the Two Treatment Groups According the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS)-R Slope.

  Responder patients were defined as those subjects showing an improvement of at least 15% in the ALSFRS-R slope during the treatment period as compared to the lead-in period.

  1 year

Secondary Outcomes (7)

• Forced Vital Capacity (FVC) %

  1 year

• SF-36 Quality of Life Rating Scale

  1 year

• Time to Tracheostomy From Starting of Study Medication Dosing (if Appropriate)

  1 year

• Survival Time From Starting of Study Medication Dosing (if Appropriate)

  1 year

• ALSFRS-R at Study End

  1 year

Study Arms (2)

TUDCA

EXPERIMENTAL

tauroursodeoxycholic acid di-hydrate

Drug: tauroursodeoxycholic acid (TUDCA)

placebo

PLACEBO COMPARATOR

excipient lactose

Drug: Placebo

Interventions

tauroursodeoxycholic acid (TUDCA) DRUG

Oral route at the dose of 1 g b.i.d. (2 g daily) for 1 year

Also known as: Ursodiol, Actigall, Generic

TUDCA

Placebo DRUG

identical placebo by oral route at the same dosing schedule

Also known as: Oral route at the dose of 1 g b.i.d. (2 g daily) for 1 year

placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Caucasian male or female out-patients;
• aged 18 to 75 years inclusive;
• diagnosis of "probable" or "definite" amyotrophic lateral sclerosis according to the El Escorial revised criteria (1);
• first symptoms of ALS by no more than 1.5 years;
• in treatment with steady regimen of riluzole for a minimum of 3 months before study entry, and desiring its continuation;
• FVC ≥ 75% of predicted;
• no conditions known to be contraindications to the use of TUDCA;
• written informed consent.

You may not qualify if:

• subjects who underwent tracheostomy;
• subjects who underwent resection of gall bladder;
• subjects with signs of conduction blocks of motor nerves, sensory nerves or both on nerve conduction study;
• subjects with clinical signs of dementia;
• subjects with active peptic ulcer;
• subjects with active malignancy;
• subjects with bulbar onset;
• female subjects who are pregnant or lactating
• subjects who have received an experimental drug or have participated in a clinical trial within 3 months prior to screening
• employees of the investigator or study centre with direct involvement in the proposed study or other studies under the direction of that investigator or study centre.

Sponsors & Collaborators

• Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta: lead
• University of Palermo: collaborator
• Federico II University: collaborator

Study Sites (1)

Fondazione IRCCS Istituto neurologico Carlo Besta

Milan, Milan, 20133, Italy

Location

Related Publications (42)

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MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

ursodoxicoltaurine; Ursodeoxycholic Acid; Drugs, Generic; WW Domain-Containing Oxidoreductase

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Deoxycholic Acid; Cholic Acids; Bile Acids and Salts; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholanes; Pharmaceutical Preparations; Short Chain Dehydrogenase-Reductases; NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases; Alcohol Oxidoreductases; Oxidoreductases; Enzymes; Enzymes and Coenzymes; Tumor Suppressor Proteins; Neoplasm Proteins; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Alberto Albanese
• Organization: Fondazione Istituto Neurologico Carlo Besta

alberto.albanese@unicatt.it

+39 02 2392 4552

Study Officials

• Alberto Albanese, MD

  Fondazione IRCCS Istituto neurologico Carlo Besta

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 7, 2009
• First Posted: April 8, 2009
• Study Start: June 1, 2008
• Primary Completion: July 1, 2011
• Study Completion: April 1, 2012
• Last Updated: November 26, 2014
• Results First Posted: November 26, 2014

Record last verified: 2014-11

Locations

IT (1)