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Combination Therapy in Amyotrophic Lateral Sclerosis (ALS) (PNA)

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ClinicalTrials.gov Identifier: NCT00919555
Recruitment Status : Completed
First Posted : June 12, 2009
Last Update Posted : November 30, 2012
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Drug: Pioglitazone and Tretinoin Drug: Tretinoin and Pioglitazone HCL Drug: Placebo Phase 1 Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Phase IIA Trial: Tretinoin and Pioglitazone HCL Combination Therapy in Amyotrophic Lateral Sclerosis
Study Start Date : June 2008
Actual Primary Completion Date : November 2009
Actual Study Completion Date : March 2012

Arm Intervention/treatment
Active Comparator: Tretionoin and Pioglitazone HCL
20 patients will be randomized blindedly to Tretinoin and Pioglitazone HCL
Drug: Pioglitazone and Tretinoin
Tretinoin: 1 pill twice a day (10 mg/bid) Pioglitazone HCL: 1 pill once a day (30 mg/qd)

Drug: Tretinoin and Pioglitazone HCL
Tretinoin 10 mg 1 pill po twice a day Pioglitazone HCL 30 mg 1 pill po once a day

Placebo Comparator: Sugar Pill
10 Patients will randomly receive placebo
Drug: Placebo

Primary Outcome Measures :
  1. To evaluate the safety and efficacy of Tretinoin and Pioglitazone HCL in patients with ALS [ Time Frame: 3 years ]

Secondary Outcome Measures :
  1. 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 ALSFRS [ Time Frame: 3 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00919555

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United States, Arizona
Phoenix Neurological Associates, LTD
Phoenix, Arizona, United States, 85018
Sponsors and Collaborators
Phoenix Neurological Associates, LTD
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Principal Investigator: Todd D Levine, MD Phoenix Neurological Associates, LTD
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Responsible Party: Phoenix Neurological Associates, LTD
ClinicalTrials.gov Identifier: NCT00919555    
Other Study ID Numbers: 20071808
First Posted: June 12, 2009    Key Record Dates
Last Update Posted: November 30, 2012
Last Verified: November 2012
Keywords provided by Phoenix Neurological Associates, LTD:
ALS Treatment
Pioglitazone HCL
Tau levels
Additional relevant MeSH terms:
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Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Hypoglycemic Agents
Physiological Effects of Drugs
Antineoplastic Agents
Keratolytic Agents
Dermatologic Agents