Amyotrophic Lateral SclerosisPhase 1/2PNANCT00919555
Combination Therapy in Amyotrophic Lateral Sclerosis (ALS)
A Phase 1/2 study testing Pioglitazone and Tretinoin and Tretinoin and Pioglitazone HCL in people with Amyotrophic Lateral Sclerosis, run by Phoenix Neurological Associates, LTD at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- Pioglitazone and Tretinoin and Tretinoin and Pioglitazone HCL
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2008to Mar 2012
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Phoenix Neurological Associates, LTD
Phoenix, Arizona, 85018
About this study
Official title: 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.
Read the 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
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- Pioglitazone and Tretinoin, Tretinoin and Pioglitazone HCL, Placebo
- Keywords
- ALS Treatment, Tretinoin, Pioglitazone HCL, Actos, Tau levels, ALS
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pioglitazone and TretinoinDrug
Tretinoin: 1 pill twice a day (10 mg/bid) Pioglitazone HCL: 1 pill once a day (30 mg/qd)
Tretinoin and Pioglitazone HCLDrug
Tretinoin 10 mg 1 pill po twice a day Pioglitazone HCL 30 mg 1 pill po once a day
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Tretionoin and Pioglitazone HCL | Active comparator | 20 patients will be randomized blindedly to Tretinoin and Pioglitazone HCL Receives: Drug: Pioglitazone and Tretinoin; Drug: Tretinoin and Pioglitazone HCL |
| Sugar Pill | Placebo comparator | 10 Patients will randomly receive placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the safety and efficacy of Tretinoin and Pioglitazone HCL in patients with ALS
Measured: 3 years
Secondary outcomes (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
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2009 (estimated)
- Study startJun 2008
- Primary completionNov 2009
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Phoenix Neurological Associates, LTD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Todd D Levine, MD, Principal investigator, Phoenix Neurological Associates, LTD
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00919555
- Sponsor's protocol ID
- 20071808
- Acronym
- PNA
- Status last verified
- Nov 2012
- First submitted
- 8 Jun 2009
- Last updated
- 30 Nov 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IIA Trial: Tretinoin and Pioglitazone HCL Combination Therapy in Amyotrophic Lateral Sclerosis
- ClinicalTrials.gov ID
- NCT00919555
- Acronym / sponsor ID
- PNA / 20071808
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- ALS Treatment, Tretinoin, Pioglitazone HCL, Actos, Tau levels, ALS
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Phoenix Neurological Associates, LTDUniversity, hospital or other
- Study start
- Jun 2008
- Primary completion
- Nov 2009 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 12 Jun 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tretionoin and Pioglitazone HCL | Active comparator | Drug: Pioglitazone and Tretinoin, Drug: Tretinoin and Pioglitazone HCL20 patients will be randomized blindedly to Tretinoin and Pioglitazone HCL |
| Sugar Pill | Placebo comparator | Drug: Placebo10 Patients will randomly receive placebo |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pioglitazone and TretinoinTretinoin: 1 pill twice a day (10 mg/bid) Pioglitazone HCL: 1 pill once a day (30 mg/qd) | Drug | Tretionoin and Pioglitazone HCL |
| Tretinoin and Pioglitazone HCLTretinoin 10 mg 1 pill po twice a day Pioglitazone HCL 30 mg 1 pill po once a day | Drug | Tretionoin and Pioglitazone HCL |
| PlaceboPlacebo | Drug | Sugar Pill |
Primary outcome
To evaluate the safety and efficacy of Tretinoin and Pioglitazone HCL in patients with ALS
Time frame: 3 years
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Nov 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Todd D Levine, MD principal investigator
Phoenix Neurological Associates, LTD
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Pioglitazone and Tretinoin and Tretinoin and Pioglitazone HCL in people with Amyotrophic Lateral Sclerosis, run by Phoenix Neurological Associates, LTD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Nov 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate the safety and efficacy of Tretinoin and Pioglitazone HCL in patients with ALS (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Nov 2012.