A Multicenter, Dose Ranging Safety and Pharmacokinetics Study of Arimoclomol in ALS

NCT ID: NCT00244244

Last Updated: 2012-02-09

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

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-10-31

Study Completion Date

2007-01-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Amyotrophic Lateral Sclerosis (ALS)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Interventions

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arimoclomol

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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CytRx

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Merit Cudkowicz, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Jeremy Shefner, MD

Role: PRINCIPAL_INVESTIGATOR

State University of New York - Upstate Medical University

Locations

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University of California, Irvine Medical Center

Irvine, California, United States

Site Status

University of Miami School of Medicine

Miami, Florida, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Hennepin Faculty Associates/Berman Center

Minneapolis, Minnesota, United States

Site Status

SUNY Upstate Medical University

Syracuse, New York, United States

Site Status

Duke University

Durham, North Carolina, United States

Site Status

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Drexel University College of Medicine

Philadelphia, Pennsylvania, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Countries

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United States

References

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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. doi: 10.1038/nm1021. Epub 2004 Mar 21.

Reference Type BACKGROUND
PMID: 15034571 (View on PubMed)

Benn SC, Brown RH Jr. Putting the heat on ALS. Nat Med. 2004 Apr;10(4):345-7. doi: 10.1038/nm0404-345. No abstract available.

Reference Type BACKGROUND
PMID: 15057226 (View on PubMed)

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. doi: 10.1111/j.1749-6632.2002.tb04306.x.

Reference Type BACKGROUND
PMID: 12079878 (View on PubMed)

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. doi: 10.1006/exnr.2002.7945.

Reference Type BACKGROUND
PMID: 12093085 (View on PubMed)

Muchowski PJ, Wacker JL. Modulation of neurodegeneration by molecular chaperones. Nat Rev Neurosci. 2005 Jan;6(1):11-22. doi: 10.1038/nrn1587.

Reference Type BACKGROUND
PMID: 15611723 (View on PubMed)

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. doi: 10.1016/S0014-4886(03)00343-1.

Reference Type BACKGROUND
PMID: 14769355 (View on PubMed)

Other Identifiers

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AALS-001

Identifier Type: -

Identifier Source: org_study_id

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