Efficacy and Tolerability of Tauroursodeoxycholic Acid in Amyotrophic Lateral Sclerosis (TUDCA-ALS)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2012 by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
University of Palermo
Federico II University
Information provided by (Responsible Party):
Alberto Albanese, Istittuto Nazionale Neurologico Carlo Besta
ClinicalTrials.gov Identifier:
NCT00877604
First received: April 7, 2009
Last updated: March 23, 2012
Last verified: March 2012
  Purpose

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. 20 patients affected by ALS with site of onset in the limbs will be recruited.

All enrolled subjects will continue receiving riluzole and vitamin E 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. Primary evaluation parameter will be the ALSFRS-R (2) according to the consensus conference on designing and implementing clinical trials in ALS (3). Primary endpoint will be the ALSFRS-R slope during the treatment period as compared to the lead-in period.

Efficacy. Secondary parameters will include 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) and the number of patients showing an improvement ≥ 15% in ALSFRS-R slope as compared to the lead-in period (responders).

Safety. Incidence, severity and type of adverse events; changes in clinical laboratory findings.


Condition Intervention Phase
Amyotrophic Lateral Sclerosis
Drug: tauroursodeoxycholic acid (TUDCA)
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind Multicenter Pilot Study vs. Placebo for the Evaluation of Efficacy and Tolerability of Tauroursodeoxycholic Acid Administered by Oral Route as Add on Treatment in Patients Affected by Amyotrophic Lateral Sclerosis

Resource links provided by NLM:


Further study details as provided by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta:

Primary Outcome Measures:
  • Amyotrophic Lateral Sclerosis functional rating scale (ALSFRS)-R slope [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Forced vital capacity (FVC) % [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • SF-36 quality of life rating scale [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Time to tracheostomy from starting of study medication dosing (if appropriate) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Survival time from starting of study medication dosing (if appropriate) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 26
Study Start Date: June 2008
Estimated Study Completion Date: April 2012
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TUDCA Drug: tauroursodeoxycholic acid (TUDCA)
Oral route at the dose of 1 g b.i.d. (2 g daily) for 1 year
Other Names:
  • Ursodiol
  • Actigall
  • Generic
Placebo Comparator: placebo Drug: Placebo
identical placebo by oral route at the same dosing schedule

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 and vitamin E 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.

Exclusion Criteria:

  • 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;
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00877604

Locations
Italy
Fondazione IRCCS Istituto neurologico Carlo Besta
Milan, Italy, 20133
Sponsors and Collaborators
Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
University of Palermo
Federico II University
Investigators
Principal Investigator: Alberto Albanese, MD Fondazione IRCCS Istituto neurologico Carlo Besta
  More Information

Publications:

Responsible Party: Alberto Albanese, Professor, Istittuto Nazionale Neurologico Carlo Besta
ClinicalTrials.gov Identifier: NCT00877604     History of Changes
Other Study ID Numbers: TUDCA200701, EudraCT No.: 2007-001592-10
Study First Received: April 7, 2009
Last Updated: March 23, 2012
Health Authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health

Keywords provided by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta:
ALS
Therapy
Tauroursodeoxycholic acid
TUDCA
antioxidant
antiapoptotic drug
neuroprotective drug

Additional relevant MeSH terms:
Amyotrophic Lateral Sclerosis
Sclerosis
Motor Neuron Disease
Central Nervous System Diseases
Metabolic Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neuromuscular Diseases
Pathologic Processes
Proteostasis Deficiencies
Spinal Cord Diseases
TDP-43 Proteinopathies
Taurochenodeoxycholic Acid
Tauroursodeoxycholic acid
Anti-Infective Agents
Antiviral Agents
Cholagogues and Choleretics
Gastrointestinal Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014