Clinical trial NCT00244244: A Multicenter, Dose Ranging Safety and Pharmacokinetics Study of Arimoclomol in ALS
Official title: A Multicenter, Dose Ranging Safety and Pharmacokinetics Study of Arimoclomol in Amyotrophic Lateral Sclerosis (ALS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Amyotrophic Lateral Sclerosis (ALS)
Lead sponsor: CytRx
Sponsor class: INDUSTRY
First posted: 2005-10-26
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Safety
Secondary outcomes:
measure: Pharmacokinetics
measure: ALSFRS-R
measure: Vital Capacity
Other outcomes:
Locations:
city: Irvine
country: United States
facility: University of California, Irvine Medical Center
state: California
city: Miami
country: United States
facility: University of Miami School of Medicine
state: Florida
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: Hennepin Faculty Associates/Berman Center
state: Minnesota
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Drexel University College of Medicine
state: Pennsylvania
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
Study officials:
affiliation: Massachusetts General Hospital
name: Merit Cudkowicz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: State University of New York - Upstate Medical University
name: Jeremy Shefner, MD
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1038/nm1021. Epub 2004 Mar 21.
citation: 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.
citation: 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.
citation: 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.
citation: Muchowski PJ, Wacker JL. Modulation of neurodegeneration by molecular chaperones. Nat Rev Neurosci. 2005 Jan;6(1):11-22. doi: 10.1038/nrn1587.
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. doi: 10.1016/S0014-4886(03)00343-1.