A Multicenter, Dose Ranging Safety and Pharmacokinetics Study of Arimoclomol in ALS - Full Text View

Purpose

The primary purpose of this study is to evaluate the safety and tolerability of arimoclomol in ALS patients following 90 days of dosing. In addition, the amount of arimoclomol in blood and cerebrospinal fluid will be measured.

Condition	Intervention	Phase
Amyotrophic Lateral Sclerosis (ALS)	Drug: arimoclomol	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Double-Blind Primary Purpose: Treatment
Official Title:	A Multicenter, Dose Ranging Safety and Pharmacokinetics Study of Arimoclomol in Amyotrophic Lateral Sclerosis (ALS)

Resource links provided by NLM:

Genetics Home Reference related topics: amyotrophic lateral sclerosis

MedlinePlus related topics: Amyotrophic Lateral Sclerosis

U.S. FDA Resources

Further study details as provided by CytRx:

Primary Outcome Measures:

Safety

Secondary Outcome Measures:

Pharmacokinetics
ALSFRS-R
Vital Capacity

Estimated Enrollment:	80
Study Start Date:	October 2005
Study Completion Date:	January 2007
Primary Completion Date:	January 2007 (Final data collection date for primary outcome measure)

Detailed Description:

Arimoclomol is a small molecule that upregulates "molecular chaperones" in cells under stress. Arimoclomol extends survival by five weeks when given both pre-symptomatically and at disease onset in a mutant superoxide dismutase (SOD1) transgenic mouse model of ALS. Furthermore, it has been demonstrated to have neuroprotective and neuroregenerative effects in other rat models of nerve damage. Molecular chaperone proteins are critical in the cellular response to stress and protein misfolding. Recent data suggest that the SOD1 mutation responsible for ALS in some patients with familial disease reduces the availability of a variety of molecular chaperones, and thus weakens their ability to respond to cellular stress. Protein misfolding and consequent aggregation may play a role in the pathogenesis of both the familial and sporadic forms of ALS. Therapeutic agents such as arimoclomol that improve cellular chaperone response to protein misfolding may be helpful in ALS.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Familial or sporadic ALS
Vital capacity equal to or more than 60% predicted value for gender, height and age at the screening visit
First ALS symptoms occurred no more than five years prior to screening
Must be able to take oral medication

Exclusion Criteria:

Dependence on mechanical ventilation

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00244244

Locations

United States, California
University of California, Irvine Medical Center
Irvine, California, United States, 92868
United States, Florida
University of Miami School of Medicine
Miami, Florida, United States, 33136
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02129
United States, Minnesota
Hennepin Faculty Associates/Berman Center
Minneapolis, Minnesota, United States, 55404
United States, New York
SUNY Upstate Medical University
Syracuse, New York, United States, 13210
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27705
United States, Pennsylvania
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Drexel University College of Medicine
Philadelphia, Pennsylvania, United States, 19107
United States, Texas
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229

Sponsors and Collaborators

CytRx

Investigators

Principal Investigator:	Merit Cudkowicz, MD	Massachusetts General Hospital
Principal Investigator:	Jeremy Shefner, MD	State University of New York - Upstate Medical University

More Information

Publications:

Kieran D, Kalmar B, Dick JR, Riddoch-Contreras J, Burnstock G, Greensmith L. Treatment with arimoclomol, a coinducer of heat shock proteins, delays disease progression in ALS mice. Nat Med. 2004 Apr;10(4):402-5. Epub 2004 Mar 21.

Benn SC, Brown RH Jr. Putting the heat on ALS. Nat Med. 2004 Apr;10(4):345-7. No abstract available.

Kurthy M, Mogyorosi T, Nagy K, Kukorelli T, Jednakovits A, Talosi L, Biro K. Effect of BRX-220 against peripheral neuropathy and insulin resistance in diabetic rat models. Ann N Y Acad Sci. 2002 Jun;967:482-9.

Kalmar B, Burnstock G, Vrbova G, Urbanics R, Csermely P, Greensmith L. Upregulation of heat shock proteins rescues motoneurones from axotomy-induced cell death in neonatal rats. Exp Neurol. 2002 Jul;176(1):87-97.

Muchowski PJ, Wacker JL. Modulation of neurodegeneration by molecular chaperones. Nat Rev Neurosci. 2005 Jan;6(1):11-22. Review.

Kalmar B, Greensmith L, Malcangio M, McMahon SB, Csermely P, Burnstock G. The effect of treatment with BRX-220, a co-inducer of heat shock proteins, on sensory fibers of the rat following peripheral nerve injury. Exp Neurol. 2003 Dec;184(2):636-47.

Responsible Party:	CytRx
ClinicalTrials.gov Identifier:	NCT00244244 History of Changes
Other Study ID Numbers:	AALS-001
Study First Received:	October 25, 2005
Last Updated:	February 8, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Amyotrophic Lateral Sclerosis
Sclerosis
Motor Neuron Disease
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases

Neurodegenerative Diseases
TDP-43 Proteinopathies
Neuromuscular Diseases
Proteostasis Deficiencies
Metabolic Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on May 23, 2013