Amyotrophic Lateral SclerosisPhase 2NCT00690118
Study of Pioglitazone in Patients With Amyotrophic Lateral Sclerosis
A Phase 2 study testing pioglitazone in people with Amyotrophic Lateral Sclerosis, run by University of Ulm at 15 sites in Germany.
Trial summary
Primary objective: Efficacy of pioglitazone (45 mg/day) as add-on therapy to standard therapy with riluzole in patients with ALS compared to placebo in terms of survival (mortality defined exclusively as death). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- pioglitazone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 219 participants
- Where
- 15 sitesGermany
- Study dates
- May 2008to Jun 2010
- Phase
- Phase 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- possible, probable (clinically or laboratory) or definite ALS according to the revised version of the El Escorial World Federation of Neurology criteria
- disease duration more than 6 months and less than 3 years
- best-sitting FVC between 50% and 95% of predicted normal
- continuously treated with 100 mg riluzole daily, for at least one month
- onset of progression weakness within 36 months prior to study
- women of childbearing age be non-lactating and surgically sterile or using a highly effective method of birth control and have a negative pregnancy test
- capable of thoroughly understanding all information given and giving full informed consent according to GCP
Who cannot join
- previous participation in another clinical study within the preceding three months
- tracheotomy or assisted ventilation of any type during the preceding three months
- gastrostomy
- any medical condition known to have an association with motor neuron dysfunction which might confound or obscure the diagnosis of ALS
- presence of any concomitant life-threatening disease or impairment likely to interfere with functional assessment
- confirmed hepatic insufficiency or abnormal liver function (ASAT and/or ALAT more than 1.5 upper limit of normal)
Show all 16Show fewer
- renal insufficiency (serum creatinine more than 2.26 mg/dl)
- evidence of major psychiatric disorder or clinically evident dementia precluding evaluation of symptoms
- known hypersensitivity to any component of the study drugs
- likely to be not cooperative or comply with the trial requirements (as assessed by the investigator), or unable to be reached in the case of an emergency
- other antidiabetics
- heart failure or heart failure in the patients history (NYHA I to IV)
- history of macular oedema
- treatment with thiazolidinediones within 3 months prior to screening
- known or suspected history of alcohol and/or drug abuse
- treatment with gemfibrozil within 3 months prior to screening
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
Germany15 sites
Department of Neurology, Humboldt University
Berlin, 13353
Neurologische Universitätsklinik Bergmannsheil
Bochum, North Rhine-Westphalia, 44789
Department of Neurology, Universty of Bonn
Bonn, Nordrhrein-Westfalen, D-53105
Department of Neurology, TU Dresden
Dresden, Saxony, D-01307
Department of Neurology, University of Goettingen
Göttingen, Lower Saxony, D-37073
Department of Neurology, University of Halle-Wittenberg
Halle, Saxony-Anhalt, 06097
Department of Neurology, Medical School Hannover
Hanover, Lower Saxony, 30625
Department of Neurology, University of Jena
Jena, Thuringia, D-07747
Department of Neurology and Center for Palliative Medicine, University of Munich
Munich, Bavaria, D-81366
Department of Neurology, Universty of Muenster
Münster, North Rhine-Westphalia, D-48149
Department of Neurology, Universty of Regensburg
Regensburg, Bavaria, D-93053
Department of Neurology, University of Rostock
Rostock, Mecklenburg-Vorpommern, D-18147
Department of Neurology, University of Ulm
Ulm, Baden-Wurttemberg, 89081
Department of Neurology, Deutsche Klinik für Diagnostik
Wiesbaden, Hesse, D-65191
Department of Neurology, University of Wuerzburg
Würzburg, Bavaria, 91054
About this study
Official title: Efficacy, Safety and Tolerability Study of 45 mg Pioglitazone in Patients With Amyotrophic Lateral Sclerosis (ALS) Receiving Standard Therapy (Riluzole)
Primary objective:
Efficacy of pioglitazone (45 mg/day) as add-on therapy to standard therapy with riluzole in patients with ALS compared to placebo in terms of survival (mortality defined exclusively as death).
This is a prospective, multicentre, randomised, stratified, parallel-group, double-blind trial comparing placebo with 45 mg pioglitazone as add-on therapy to 100 mg riluzole in ALS in 220 enrolled patients. For entry, the El Escorial Criteria for diagnosis will be used. The duration of treatment will be 18 months. The primary endpoint will be subjected to a confirmatory analyses. Secondary variables will be incidence of tracheotomy or non-invasive ventilation, ALS Functional Rating Scale, Quality of life and safety variables.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- pioglitazone, placebo
- Keywords
- amyotrophic lateral sclerosis, survival time, ALS functioning Rating Scale, quality of life, non-invasive ventilation, clinical tolerability, survival
- 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.
pioglitazoneDrug
Also called Actos
45 mg/day, 18 months
placeboDrug
once daily, 18 months
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Not described Receives: Drug: pioglitazone |
| 2 | Placebo comparator | Not described Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival in patients with ALS treated with pioglitazone compared to placebo
Measured: 18 months
Secondary outcomes (1)
Incidence of tracheotomy or non-invasive ventilation
Measured: 18 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2008 (estimated)
- Study startMay 2008
- Primary completionJun 2010
- Study completionJun 2010
Why it stopped: The interim analysis showed no tendency in favour of the verum group. Therefore it was decided to stop the study prematurely.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 219 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Ulm
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Albert Christian Ludolph, Prof., University of Ulm
- Investigators
- Albert C Ludolph, MD, Prof., Principal investigator, Department of Neurology, University of Ulm
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00690118
- Sponsor's protocol ID
- GERP ALS
- Other IDs
- EUDRACT NUMBER 2006-005410-13
- Status last verified
- May 2015
- First submitted
- 2 Jun 2008
- Last updated
- 29 May 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Schutz B, Reimann J, Dumitrescu-Ozimek L, Kappes-Horn K, Landreth GE, Schurmann B, Zimmer A, Heneka MT. The oral antidiabetic pioglitazone protects from neurodegeneration and amyotrophic lateral sclerosis-like symptoms in superoxide dismutase-G93A transgenic mice. J Neurosci. 2005 Aug 24;25(34):7805-12. doi: 10.1523/JNEUROSCI.2038-05.2005.
PubMed 16120782Kiaei M, Kipiani K, Chen J, Calingasan NY, Beal MF. Peroxisome proliferator-activated receptor-gamma agonist extends survival in transgenic mouse model of amyotrophic lateral sclerosis. Exp Neurol. 2005 Feb;191(2):331-6. doi: 10.1016/j.expneurol.2004.10.007.
PubMed 15649489Dupuis L, Dengler R, Heneka MT, Meyer T, Zierz S, Kassubek J, Fischer W, Steiner F, Lindauer E, Otto M, Dreyhaupt J, Grehl T, Hermann A, Winkler AS, Bogdahn U, Benecke R, Schrank B, Wessig C, Grosskreutz J, Ludolph AC; GERP ALS Study Group. A randomized, double blind, placebo-controlled trial of pioglitazone in combination with riluzole in amyotrophic lateral sclerosis. PLoS One. 2012;7(6):e37885. doi: 10.1371/journal.pone.0037885. Epub 2012 Jun 8.
PubMed 22715372
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy, Safety and Tolerability Study of 45 mg Pioglitazone in Patients With Amyotrophic Lateral Sclerosis (ALS) Receiving Standard Therapy (Riluzole)
- ClinicalTrials.gov ID
- NCT00690118
- Acronym / sponsor ID
- GERP ALS
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- amyotrophic lateral sclerosis, survival time, ALS functioning Rating Scale, quality of life, non-invasive ventilation, clinical tolerability, survival
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The interim analysis showed no tendency in favour of the verum group. Therefore it was decided to stop the study prematurely.
- Enrolment
- 219 participants (actual)
- Lead sponsor
- University of UlmUniversity, hospital or other
- Study start
- May 2008
- Primary completion
- Jun 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 4 Jun 2008 (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.
Primary objective:
Efficacy of pioglitazone (45 mg/day) as add-on therapy to standard therapy with riluzole in patients with ALS compared to placebo in terms of survival (mortality defined exclusively as death).
This is a prospective, multicentre, randomised, stratified, parallel-group, double-blind trial comparing placebo with 45 mg pioglitazone as add-on therapy to 100 mg riluzole in ALS in 220 enrolled patients. For entry, the El Escorial Criteria for diagnosis will be used. The duration of treatment will be 18 months. The primary endpoint will be subjected to a confirmatory analyses. Secondary variables will be incidence of tracheotomy or non-invasive ventilation, ALS Functional Rating Scale, Quality of life and safety variables.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: pioglitazone |
| 2 | Placebo comparator | Drug: placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- possible, probable (clinically or laboratory) or definite ALS according to the revised version of the El Escorial World Federation of Neurology criteria
- disease duration more than 6 months and less than 3 years
- best-sitting FVC between 50% and 95% of predicted normal
- continuously treated with 100 mg riluzole daily, for at least one month
- onset of progression weakness within 36 months prior to study
Key exclusion criteria (16 listed)
- previous participation in another clinical study within the preceding three months
- tracheotomy or assisted ventilation of any type during the preceding three months
- gastrostomy
- any medical condition known to have an association with motor neuron dysfunction which might confound or obscure the diagnosis of ALS
- presence of any concomitant life-threatening disease or impairment likely to interfere with functional assessment
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 |
|---|---|---|
| pioglitazoneAlso: Actos45 mg/day, 18 months | Drug | 1 |
| placeboonce daily, 18 months | Drug | 2 |
Primary outcome
Survival in patients with ALS treated with pioglitazone compared to placebo
Time frame: 18 months
1 secondary outcome
Incidence of tracheotomy or non-invasive ventilation
Time frame: 18 month
Results and safety
The study was stopped early (reason given: The interim analysis showed no tendency in favour of the verum group. Therefore it was decided to stop the study prematurely.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2015.
- Background: PubMed 16120782Schutz B, Reimann J, Dumitrescu-Ozimek L, Kappes-Horn K, Landreth GE, Schurmann B, Zimmer A, Heneka MT. The oral antidiabetic pioglitazone protects from neurodegeneration and amyotrophic lateral sclerosis-like symptoms in superoxide dismutase-G93A transgenic mice. J Neurosci. 2005 Aug 24;25(34):7805-12. doi: 10.1523/JNEUROSCI.2038-05.2005.
- Background: PubMed 15649489Kiaei M, Kipiani K, Chen J, Calingasan NY, Beal MF. Peroxisome proliferator-activated receptor-gamma agonist extends survival in transgenic mouse model of amyotrophic lateral sclerosis. Exp Neurol. 2005 Feb;191(2):331-6. doi: 10.1016/j.expneurol.2004.10.007.
- Derived from this study: PubMed 22715372Dupuis L, Dengler R, Heneka MT, Meyer T, Zierz S, Kassubek J, Fischer W, Steiner F, Lindauer E, Otto M, Dreyhaupt J, Grehl T, Hermann A, Winkler AS, Bogdahn U, Benecke R, Schrank B, Wessig C, Grosskreutz J, Ludolph AC; GERP ALS Study Group. A randomized, double blind, placebo-controlled trial of pioglitazone in combination with riluzole in amyotrophic lateral sclerosis. PLoS One. 2012;7(6):e37885. doi: 10.1371/journal.pone.0037885. Epub 2012 Jun 8.
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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.
Albert C Ludolph, MD, Prof. principal investigator
Department of Neurology, University of Ulm
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing pioglitazone in people with Amyotrophic Lateral Sclerosis, run by University of Ulm at 15 sites in Germany.
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 7 inclusion and 16 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: stopped early, as of the sponsor's last update on 29 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Germany. 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 phase mean?
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 was stopped early (reason given: The interim analysis showed no tendency in favour of the verum group. Therefore it was decided to stop the study prematurely.). Results are not available in the source record.
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?
Survival in patients with ALS treated with pioglitazone compared to placebo (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00690118, which also lists 3 linked publications.
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 29 May 2015.