Arterial Occlusive DiseasePhase 2/3NCT00153166
ARREST PAD (Peripheral Arterial Disease)
A Phase 2/3 study testing atorvastatin and pioglitazone in people with Arterial Occlusive Disease and Intermittent Claudication, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
This trial will test the hypothesis that inflammation and insulin resistance contribute to reduced walking distance in subjects with intermittent claudication by impairing vascular reactivity and skeletal muscle metabolic function. Read more about this study
- Who is it for?
- Ages 40 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Arterial Occlusive Disease, Intermittent Claudication, Insulin Resistance
- What is being tested?
- atorvastatin and pioglitazone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 76 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2004to Dec 2011
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 40 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- symptomatic intermittent claudication for >= 6 months
- resting ankle/brachial index (ABI) <=0.90
- maximal treadmill walking time between 1-20 minutes
- >= 20% decrease in ABI post treadmill exercise
- 4 week statin wash-out prior to initial study testing (if applicable)
Who cannot join
- myocardial infarction or coronary artery bypass surgery within past 6 months
- lower extremity revascularization (surgical or percutaneous) within past 6 months
- transient ischemic attack or ischemic stroke within past 6 months
- pregnancy
- uncontrolled hypertension (systolic pressure > 180mmHg and/or diastolic pressure > 100mmHg
- serum creatinine >2.5
Show all 11Show fewer
- hepatic transaminases (AST, ALT) > 3x upper limit of normal (ULN)
- creatine kinase > 5x ULN
- known hypersensitivity to HMG-CoA reductase inhibitors
- insulin dependent Type 2 diabetes
- current treatment with thiazolidinedione
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham & Women's Hospital
Boston, Massachusetts, 02115
About this study
Official title: The Contribution of Inflammation and Insulin Resistance to Intermittent Claudication
This trial will test the hypothesis that inflammation and insulin resistance contribute to reduced walking distance in subjects with intermittent claudication by impairing vascular reactivity and skeletal muscle metabolic function.
Read the detailed description
People with peripheral arterial disease (PAD), an important clinical manifestation of atherosclerosis, often suffer symptoms of intermittent claudication that impair their walking ability and adversely affect their quality of life. People with PAD are also at increased risk for adverse cardiovascular events, including myocardial infarction, stroke and death. Unfortunately, medical therapies directed to the functional and limb-threatening manifestations are limited. Little attention has been paid to the biologic processes that cause PAD, and to atherogenic mechanisms that may preferentially affect the peripheral circulation.
Vascular inflammation and insulin resistance are two important and interdependent conditions that are associated with atherosclerosis. Subjects in this trial (160 adults with stable intermittent claudication who are not taking insulin or insulin-sensitizing medications, such as thiazolidinediones) will be randomized in a placebo-controlled, parallel design manner, to atorvastatin 80 mg orally daily (to reduce inflammation) and pioglitazone 45 mg orally once daily (to improve insulin sensitivity). Forty healthy adult subjects, age and gender-matched to a subset of the study group, will be enrolled to serve as a control population. Primary and secondary study endpoints include: treadmill walking time, endothelium-dependent vasodilation, and insulin-mediated skeletal muscle glucose uptake.
- Being tested
- atorvastatin and pioglitazone, atorvastatin/placebo, pioglitazone/placebo, placebo/placebo
- Keywords
- peripheral arterial disease, intermittent claudication
- Medical subject headings
- Arterial Occlusive Diseases, Intermittent Claudication, Insulin Resistance, Peripheral Arterial Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
atorvastatin and pioglitazoneDrug
Also called atorvastatin: lipitor, pioglitazone: actos
atorvastatin 80 mg orally once daily (to reduce inflammation) and pioglitazone 30 mg orally once daily (to improve insulin sensitivity)
atorvastatin/placeboDrug
Also called atorvastatin: lipitor
atorvastatin 80 mg orally once daily and matching placebo orally twice daily
pioglitazone/placeboDrug
Also called pioglitazone: actos
pioglitazone 30 mg orally once daily and matching placebo orally once daily
placebo/placeboDrug
placebo orally three times daily
| Study group | Role | What they receive |
|---|---|---|
| Patients with PAD (Including diabetics) | Experimental | Randomized to either atorvastatin and pioglitazone, atorvastatin/placebo, pioglitazone/placebo, or placebo/placebo. Receives: Drug: atorvastatin and pioglitazone; Drug: atorvastatin/placebo; Drug: pioglitazone/placebo; Drug: placebo/placebo |
| PAD (Excluding Diabetics) | Active comparator | Randomized to either atorvastatin and pioglitazone, atorvastatin/placebo, pioglitazone/placebo, or placebo/placebo. Receives: Drug: atorvastatin and pioglitazone; Drug: atorvastatin/placebo; Drug: pioglitazone/placebo; Drug: placebo/placebo |
| Healthy Controls | Active comparator | Randomized to either atorvastatin and pioglitazone, atorvastatin/placebo, pioglitazone/placebo, or placebo/placebo. Receives: Drug: atorvastatin and pioglitazone; Drug: atorvastatin/placebo; Drug: pioglitazone/placebo; Drug: placebo/placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lower Extremity Skeletal Muscle Glucose Uptake
Net calf skeletal muscle glucose uptake determined by Patlak modeling.
Measured: 60 minutes
Secondary outcomes (1)
'M' = Whole Body Insulin Sensitivity
A hyperinsulinemic-euglycemic clamp was performed prior to and during FDG-PET imaging to measure insulin sensitivity and to standardize metabolic conditions. Subjects were required to fast for 8 hours prior to the study. Patients were given a primed insulin infusion of 2 mU/kg/min. Serum glucose measurements were made at five-minute intervals from an arterialized venous sample achieved by placing the hand in a warming box at 50°C. Blood glucose levels are checked every 5 minutes and 20% dextrose infusion is adjusted to maintain a serum glucose level of approximately 80 mg/dL. Subjects were considered to have achieved steady state when the dextrose infusion rate required to maintain a serum glucose level of 80 mg/dL varied by no greater than 5%. To compute the steady-state glucose disposal rate, we averaged the glucose infusion rates over the last 20 minutes of the clamp and applied a "space correction" to account for small changes in serum glucose levels over that time period.
Measured: every 5 minutes for 20 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2005 (estimated)
- Study startJan 2004
- Primary completionNov 2010
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Arterial Occlusive DiseaseStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Mark Alan Creager, MD, Brigham and Women's Hospital
- Investigators
- Mark Creager, M.D., Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00153166
- Sponsor's protocol ID
- 2003P-001501
- Other IDs
- R01HL075771
- Status last verified
- Sep 2014
- First submitted
- 8 Sep 2005
- Last updated
- 30 Sep 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Pande RL, Brown J, Buck S, Redline W, Doyle J, Plutzky J, Creager MA. Association of monocyte tumor necrosis factor alpha expression and serum inflammatory biomarkers with walking impairment in peripheral artery disease. J Vasc Surg. 2015 Jan;61(1):155-61. doi: 10.1016/j.jvs.2014.06.116. Epub 2014 Aug 2.
PubMed 25095746
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Contribution of Inflammation and Insulin Resistance to Intermittent Claudication
- ClinicalTrials.gov ID
- NCT00153166
- Acronym / sponsor ID
- 2003P-001501
- Keywords
- peripheral arterial disease, intermittent claudication
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Jan 2004
- Primary completion
- Nov 2010 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 12 Sep 2005 (estimated)
- Results
- Posted 30 Sep 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial will test the hypothesis that inflammation and insulin resistance contribute to reduced walking distance in subjects with intermittent claudication by impairing vascular reactivity and skeletal muscle metabolic function.
Detailed description
People with peripheral arterial disease (PAD), an important clinical manifestation of atherosclerosis, often suffer symptoms of intermittent claudication that impair their walking ability and adversely affect their quality of life. People with PAD are also at increased risk for adverse cardiovascular events, including myocardial infarction, stroke and death. Unfortunately, medical therapies directed to the functional and limb-threatening manifestations are limited. Little attention has been paid to the biologic processes that cause PAD, and to atherogenic mechanisms that may preferentially affect the peripheral circulation.
Vascular inflammation and insulin resistance are two important and interdependent conditions that are associated with atherosclerosis. Subjects in this trial (160 adults with stable intermittent claudication who are not taking insulin or insulin-sensitizing medications, such as thiazolidinediones) will be randomized in a placebo-controlled, parallel design manner, to atorvastatin 80 mg orally daily (to reduce inflammation) and pioglitazone 45 mg orally once daily (to improve insulin sensitivity). Forty healthy adult subjects, age and gender-matched to a subset of the study group, will be enrolled to serve as a control population. Primary and secondary study endpoints include: treadmill walking time, endothelium-dependent vasodilation, and insulin-mediated skeletal muscle glucose uptake.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Patients with PAD (Including diabetics) | Experimental | Drug: atorvastatin and pioglitazone, Drug: atorvastatin/placebo, Drug: pioglitazone/placebo, Drug: placebo/placeboRandomized to either atorvastatin and pioglitazone, atorvastatin/placebo, pioglitazone/placebo, or placebo/placebo. |
| PAD (Excluding Diabetics) | Active comparator | Drug: atorvastatin and pioglitazone, Drug: atorvastatin/placebo, Drug: pioglitazone/placebo, Drug: placebo/placeboRandomized to either atorvastatin and pioglitazone, atorvastatin/placebo, pioglitazone/placebo, or placebo/placebo. |
| Healthy Controls | Active comparator | Drug: atorvastatin and pioglitazone, Drug: atorvastatin/placebo, Drug: pioglitazone/placebo, Drug: placebo/placeboRandomized to either atorvastatin and pioglitazone, atorvastatin/placebo, pioglitazone/placebo, or placebo/placebo. |
Who may qualify
- Ages
- 40 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- symptomatic intermittent claudication for >= 6 months
- resting ankle/brachial index (ABI) <=0.90
- maximal treadmill walking time between 1-20 minutes
- >= 20% decrease in ABI post treadmill exercise
- 4 week statin wash-out prior to initial study testing (if applicable)
Key exclusion criteria (11 listed)
- myocardial infarction or coronary artery bypass surgery within past 6 months
- lower extremity revascularization (surgical or percutaneous) within past 6 months
- transient ischemic attack or ischemic stroke within past 6 months
- pregnancy
- uncontrolled hypertension (systolic pressure > 180mmHg and/or diastolic pressure > 100mmHg
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 |
|---|---|---|
| atorvastatin and pioglitazoneAlso: atorvastatin: lipitor, pioglitazone: actosatorvastatin 80 mg orally once daily (to reduce inflammation) and pioglitazone 30 mg orally once daily (to improve insulin sensitivity) | Drug | Healthy Controls, PAD (Excluding Diabetics), Patients with PAD (Including diabetics) |
| atorvastatin/placeboAlso: atorvastatin: lipitoratorvastatin 80 mg orally once daily and matching placebo orally twice daily | Drug | Healthy Controls, PAD (Excluding Diabetics), Patients with PAD (Including diabetics) |
| pioglitazone/placeboAlso: pioglitazone: actospioglitazone 30 mg orally once daily and matching placebo orally once daily | Drug | Healthy Controls, PAD (Excluding Diabetics), Patients with PAD (Including diabetics) |
| placebo/placeboplacebo orally three times daily | Drug | Healthy Controls, PAD (Excluding Diabetics), Patients with PAD (Including diabetics) |
Primary outcome
Lower Extremity Skeletal Muscle Glucose Uptake
Time frame: 60 minutes
Net calf skeletal muscle glucose uptake determined by Patlak modeling.
1 secondary outcome
'M' = Whole Body Insulin Sensitivity
Time frame: every 5 minutes for 20 minutes
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25095746Pande RL, Brown J, Buck S, Redline W, Doyle J, Plutzky J, Creager MA. Association of monocyte tumor necrosis factor alpha expression and serum inflammatory biomarkers with walking impairment in peripheral artery disease. J Vasc Surg. 2015 Jan;61(1):155-61. doi: 10.1016/j.jvs.2014.06.116. Epub 2014 Aug 2.
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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.
Mark Creager, M.D. principal investigator
Brigham and Women's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing atorvastatin and pioglitazone in people with Arterial Occlusive Disease and Intermittent Claudication, run by Brigham and Women's Hospital 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 5 inclusion and 11 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 Sep 2014. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Sep 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Lower Extremity Skeletal Muscle Glucose Uptake (time frame: 60 minutes). 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 NCT00153166, which also lists 1 linked publication.
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 Sep 2014.