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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Phoenix Neurological Associates, LTD
ClinicalTrials.gov Identifier:
NCT00919555
First received: June 8, 2009
Last updated: November 29, 2012
Last verified: November 2012
  Purpose

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 Intervention Phase
Amyotrophic Lateral Sclerosis
Drug: Pioglitazone and Tretinoin
Drug: Tretinoin and Pioglitazone HCL
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Phase IIA Trial: Tretinoin and Pioglitazone HCL Combination Therapy in Amyotrophic Lateral Sclerosis

Resource links provided by NLM:


Further study details as provided by Phoenix Neurological Associates, LTD:

Primary Outcome Measures:
  • To evaluate the safety and efficacy of Tretinoin and Pioglitazone HCL in patients with ALS [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 28
Study Start Date: June 2008
Study Completion Date: March 2012
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00919555

Locations
United States, Arizona
Phoenix Neurological Associates, LTD
Phoenix, Arizona, United States, 85018
Sponsors and Collaborators
Phoenix Neurological Associates, LTD
Investigators
Principal Investigator: Todd D Levine, MD Phoenix Neurological Associates, LTD
  More Information

Additional Information:
No publications provided

Responsible Party: Phoenix Neurological Associates, LTD
ClinicalTrials.gov Identifier: NCT00919555     History of Changes
Other Study ID Numbers: 20071808
Study First Received: June 8, 2009
Last Updated: November 29, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Phoenix Neurological Associates, LTD:
ALS Treatment
Tretinoin
Pioglitazone HCL
Actos
Tau levels
ALS

Additional relevant MeSH terms:
Amyotrophic Lateral Sclerosis
Motor Neuron Disease
Sclerosis
Central Nervous System Diseases
Metabolic Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neuromuscular Diseases
Pathologic Processes
Proteostasis Deficiencies
Spinal Cord Diseases
TDP-43 Proteinopathies
Pioglitazone
Tretinoin
Antineoplastic Agents
Dermatologic Agents
Hypoglycemic Agents
Keratolytic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014