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

Amyotrophic Lateral Sclerosis (ALS) Clinical Trial

Official title:

A Multicenter, Dose Ranging Safety and Pharmacokinetics Study of Arimoclomol in Amyotrophic Lateral Sclerosis (ALS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00244244
• Other study ID #: AALS-001
• Status: Completed
• Phase: Phase 2
• First received: October 25, 2005
• Last updated: February 8, 2012
• Start date: October 2005
• Est. completion date: January 2007

Study information

• Verified date: February 2012
• Source: CytRx
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: January 2007
• Est. primary completion date: January 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Amyotrophic Lateral Sclerosis (ALS)
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• arimoclomol

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
CytRx

Country where clinical trial is conducted

United States, 

References & Publications (6)

Benn SC, Brown RH Jr. Putting the heat on ALS. Nat Med. 2004 Apr;10(4):345-7. — View Citation

Kalmar B, Burnstock G, Vrbová 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. — View Citation

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. — View Citation

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. — View Citation

Kürthy M, Mogyorósi T, Nagy K, Kukorelli T, Jednákovits A, Tálosi L, Bíró 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. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety
Secondary	Pharmacokinetics
Secondary	ALSFRS-R
Secondary	Vital Capacity