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Combination Therapy in Amyotrophic Lateral Sclerosis (ALS)

Phase 1
Completed
Conditions
Amyotrophic Lateral Sclerosis
Interventions
Registration Number
NCT00919555
Lead Sponsor
Phoenix Neurological Associates, LTD
Brief Summary

The purpose of the study is to determine the safety and the efficacy of Tretinoin and Pioglitazone HCL in patients with ALS who are currently on Riluzole.

Detailed Description

Physicians at Phoenix Neurological Associates (PNA) are looking for individuals diagnosed with ALS to participate in a double-blind, placebo controlled study of Tretinoin and Pioglitazone HCL, used in combination with Riluzole, for treating ALS. This investigator initiated trial conducted by Dr. Todd Levine and Dr. David Saperstein will help determine whether Tretinoin and Pioglitazone HCL, in combination, can slow the progression of ALS.

At present, there is little to no effective therapy for ALS, nor is there a known cause. Therefore there is a tremendous unmet need for more effective therapy for this disease and that is why the physicians at PNA have been very interested in the role of developing a more active anti-excitotoxic cocktail for patients with ALS. Since recent data have suggested that inflammatory mechanisms may interact with and promote neurodegeneration (where cells in the spinal cord and brain are lost), there have been a number of anti-inflammatory treatment strategies that have been evaluated in animal models. Some studies have shown that mice that were given Pioglitazone HCL demonstrated improved muscle strength and body weight, exhibited a delayed disease onset as well as had a longer survival rate compared to non treated mice.

In addition to these studies, retinoic acids have been studied extensively in various models of the injured nervous system. These studies have shown that retinoic acids, such as Tretinoin may be neuroprotective and support axonal growth, which could in turn slow disease progression.

The purpose of this study is to determine if such a drug "cocktail" could offer the best chance of attaining a significant reduction in disease progression by utilizing currently available FDA-approved agents

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
28
Inclusion Criteria
  • El Escorial Classification of laboratory supported probable, probable, or definite ALS
  • Age 18 - 85 years
  • Male or female
  • FVC greater than or equal to 70% predicted
Exclusion Criteria
  • Patients with FVC below 1.5 L or below 70% predicted
  • History of liver disease
  • Severe renal failure (CrCl<30)
  • History of coronary artery disease requiring placement of stents, bypass surgery or previous myocardial infarction
  • EKG at baseline with evidence for previous myocardial infarction, cardiomyopathy, or arrhythmia
  • History of intolerance to Riluzole, Tretinoin, or Pioglitazone HCL
  • History of diabetes
  • Any other comorbid condition which would make completion of trial unlikely

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Tretionoin and Pioglitazone HCLTretinoin and Pioglitazone HCL20 patients will be randomized blindedly to Tretinoin and Pioglitazone HCL
Sugar PillPlacebo10 Patients will randomly receive placebo
Tretionoin and Pioglitazone HCLPioglitazone and Tretinoin20 patients will be randomized blindedly to Tretinoin and Pioglitazone HCL
Primary Outcome Measures
NameTimeMethod
To evaluate the safety and efficacy of Tretinoin and Pioglitazone HCL in patients with ALS3 years
Secondary Outcome Measures
NameTimeMethod
To determine if cerebrospinal fluid tau levels decline over the course of treatment and if the level of tau decline correlates with response in treatment measured by ALSFRS3 years

Trial Locations

Locations (1)

Phoenix Neurological Associates, LTD

🇺🇸

Phoenix, Arizona, United States

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