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

Phase IIA Trial: Tretinoin and Pioglitazone HCL Combination Therapy in Amyotrophic Lateral Sclerosis

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.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: Placebo; Drug: Pioglitazone and Tretinoin; Drug: Tretinoin and Pioglitazone HCL

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

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Phoenix Neurological Associates, LTD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / 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; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate the safety and efficacy of Tretinoin and Pioglitazone HCL in patients with ALS	3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
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	3 years

Collaborators and Investigators

• Sponsor: Phoenix Neurological Associates, LTD

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (ACTUAL): November 1, 2009
• Study Completion (ACTUAL): March 1, 2012

Study Registration Dates

• First Submitted: June 8, 2009
• First Submitted That Met QC Criteria: June 11, 2009
• First Posted (ESTIMATE): June 12, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): November 30, 2012
• Last Update Submitted That Met QC Criteria: November 29, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: ALS; Tretinoin; Actos; ALS Treatment; Pioglitazone HCL; Tau levels
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Hypoglycemic Agents; Physiological Effects of Drugs; Antineoplastic Agents; Dermatologic Agents; Keratolytic Agents; Pioglitazone; Tretinoin
• Other Study ID Numbers: 20071808