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

• Sponsor: CytRx (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00244244
• Collaborator: (none)
• Enrollment: 80
• Locations: 10
• Duration (Months): 15
• Patients Per Site: 8
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Amyotrophic Lateral Sclerosis (ALS)	Drug: arimoclomol	Phase 2

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.

Study Design

• Study Type: Interventional
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Double
• Primary Purpose: Treatment
• Official Title: A Multicenter, Dose Ranging Safety and Pharmacokinetics Study of Arimoclomol in Amyotrophic Lateral Sclerosis (ALS)
• Study Start Date: Oct 1, 2005
• Actual Primary Completion Date: Jan 1, 2007
• Actual Study Completion Date: Jan 1, 2007

Outcome Measures

Primary Outcome Measures

1. Safety []

Secondary Outcome Measures

1. Pharmacokinetics []

2. ALSFRS-R []

3. Vital Capacity []

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	University of California, Irvine Medical Center	Irvine	California	United States	92868
2	University of Miami School of Medicine	Miami	Florida	United States	33136
3	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
4	Massachusetts General Hospital	Boston	Massachusetts	United States	02129
5	Hennepin Faculty Associates/Berman Center	Minneapolis	Minnesota	United States	55404
6	SUNY Upstate Medical University	Syracuse	New York	United States	13210
7	Duke University	Durham	North Carolina	United States	27705
8	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033
9	Drexel University College of Medicine	Philadelphia	Pennsylvania	United States	19107
10	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

Study Documents (Full-Text)

None provided.

More Information

Publications

• Benn SC, Brown RH Jr. Putting the heat on ALS. Nat Med. 2004 Apr;10(4):345-7.
• 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.
• 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.
• 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.
• 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.
• Muchowski PJ, Wacker JL. Modulation of neurodegeneration by molecular chaperones. Nat Rev Neurosci. 2005 Jan;6(1):11-22. Review.

• Responsible Party: CytRx
• ClinicalTrials.gov Identifier: NCT00244244
• Other Study ID Numbers: AALS-001
• First Posted: Oct 26, 2005
• Last Update Posted: Feb 9, 2012
• Last Verified: Feb 1, 2012

• Additional relevant MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis

Study Results

No Results Posted as of Feb 9, 2012