Cardiovascular DiseasePhase 2NCT00302250
The STRETCH Study: Distensibility on Endothelial-Dependent Vasoreactivity in Subjects With Systolic Hypertension
A Phase 2 study testing ALT-711 (alagebrium chloride) in people with Cardiovascular Disease, run by Synvista Therapeutics, Inc at 1 site in United States.
Trial summary
The primary objective of the double-blind segment is to compare effects of alagebrium vs placebo on change from baseline in endothelial function, as assessed by flow-mediated vasodilation (FMD). Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Cardiovascular Disease
- What is being tested?
- ALT-711 (alagebrium chloride)
- How many people
- 70 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2006to Dec 2006
- 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 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female 50 years of age or greater.
- Diagnosed with systolic hypertension (systolic blood pressure >140 mm Hg and (less than or equal to) 200 mm Hg, and a diastolic blood pressure (less than or equal to) 95 mm Hg) and elevated pulse pressure (systolic blood pressure [SBP] minus diastolic blood pressure [DBP] greater than 60 mm Hg).
- Normal left ventricular function (ejection fraction > 55%) at baseline (Visit 3).
- Brachial artery must be able to be visualized for FMD and PPMV determinations.
- Able to perform bicycle exercise.
- Able to read, understand and sign the informed consent after the nature of the study has been explained.
- If sexually active, the subject agrees to use reliable contraception while participating in this study. If a woman, is surgically sterilized or post-menopausal, or has a negative serum pregnancy test.
Who cannot join
- Aortic stenosis, prior known coronary artery disease (including myocardial infarction), cerebrovascular accident, or peripheral vascular disease.
- Uncontrolled hypertension (SBP > 200/DBP > 95 mm Hg).
- Atrial fibrillation, diabetes mellitus treated with insulin, or chronic lung disease.
- Any additional condition(s) which, in the opinion of the investigator, would prohibit the subject from completing the study, or not be in the best interest of the subject.
- Treatment with nitrates, or a change in antihypertensive medications within the last 1 month.
- Treatment with any investigational drug within 1 month prior to study drug administration.
Show all 12Show fewer
- Previous exposure to alagebrium.
- AST (SGOT) or ALT (SGPT) > 2x normal limit.
- Serum creatinine > 2.0 mg/dL.
- Cigar/cigarette smoking.
- Necessity to use smokeless tobacco or nicotine-containing products, or to consume caffeine, alcohol, or antioxidants starting at midnight prior to study clinic visits. NOTE: Water is allowed ad libitim.
- Positive drug screen.
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins University School of Medicine
Baltimore, Maryland, 21287
About this study
Official title: Study of The Effect of Vascular Distensibility on Endothelial-Dependent Vasoreactivity in Subjects With Systolic Hypertension Before and After Receiving Oral Alagebrium or Placebo for 8 Weeks (STRETCH)
The primary objective of the double-blind segment is to compare effects of alagebrium vs placebo on change from baseline in endothelial function, as assessed by flow-mediated vasodilation (FMD).
Read the detailed description
The secondary objectives of the double-blind segment are to:
- Compare the effects of alagebrium vs placebo on the change from baseline in endothelial-mediated vasoreactivity immediately after exercise, as assessed by pulse perfusion-mediated vasodilation (PPMV).
- Confirm results observed in the single-blind segment.
- Explore several variables as potential independent predictors of vascular stiffness and endothelial function. These parameters include age, body mass index, gender, renal disease, history of cardiovascular disease, serum cholesterol, and antihypertensive medication use.
- Provide insight into nitric oxide-dependent endothelial function in the setting of increased arterial stiffness by determination of substances in the nitric oxide signaling pathway (specifically, levels of serum cGMP; serum nitrate and nitrite; and serum asymmetric dimethylarginine [ADMA], an endogenous inhibitor of nitric oxide synthase).
- Provide insight into the relationship between AGE levels (AGE markers: pentosidine, furosine), collagen metabolism (collagen markers: procollagen I carboxyterminal propeptide [PICP], procollagen type I N terminal propeptide [PINP], cross-linked carboxyterminal telopeptide of Type I collagen [ICTP], n-terminal propeptide of type III procollagen [PIIINP]), and endothelial function; and insight into the changes in these markers in response to treatment with an AGE cross-link breaker (alagebrium).
- Provide insight into the relationship between markers of inflammation [specifically, free and total serum matrix metalloproteinase-1(MMP-1), free tissue inhibitor of metalloproteinase 1 (TIMP1), intercellular adhesion molecule-1 (ICAM), vascular cellular adhesion molecule (VCAM), P-selectin, von Willebrand factor (vWf), interleukin-6 (IL-6), endothelin 1, VEGF, NFkβ, TGF-β, IGF-1 and high-sensitivity C reactive protein (hs CRP)] and endothelial function; and insight into the changes in these markers in response to treatment with an AGE cross-link breaker (alagebrium).
- Conditions
- Cardiovascular Disease
- Being tested
- ALT-711 (alagebrium chloride)
- Keywords
- Cardiovascular, Flow-mediated vasodilation (FMD), Pulse perfusion-mediated vasodilation (PPMV), Endothelial function, Heart failure
- Medical subject headings
- Cardiovascular Diseases, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALT-711 (alagebrium chloride)Drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2006 (estimated)
- Study startFeb 2006
- Study completionDec 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseaseStudies 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
- Double blind
- Enrolment
- 70 participants
Sponsor and investigators
- Lead sponsor
- Synvista Therapeutics, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Institutes of Health (NIH), National Heart and Lung Institute
- Investigators
- Susan Zieman, MD, PhD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00302250
- Sponsor's protocol ID
- ALT-711-0217 (Amended)
- Status last verified
- Mar 2006
- First submitted
- 13 Mar 2006
- Last updated
- 22 Mar 2006
- Results posted
- No
Publications
Little WC, Zile MR, Kitzman DW, Hundley WG, O'Brien TX, Degroof RC. The effect of alagebrium chloride (ALT-711), a novel glucose cross-link breaker, in the treatment of elderly patients with diastolic heart failure. J Card Fail. 2005 Apr;11(3):191-5. doi: 10.1016/j.cardfail.2004.09.010.
PubMed 15812746Kass DA, Shapiro EP, Kawaguchi M, Capriotti AR, Scuteri A, deGroof RC, Lakatta EG. Improved arterial compliance by a novel advanced glycation end-product crosslink breaker. Circulation. 2001 Sep 25;104(13):1464-70. doi: 10.1161/hc3801.097806.
PubMed 11571237Liu ZR, Ting CT, Zhu SX, Yin FC. Aortic compliance in human hypertension. Hypertension. 1989 Aug;14(2):129-36. doi: 10.1161/01.hyp.14.2.129.
PubMed 2759675Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, Herrington D, Vallance P, Vita J, Vogel R; International Brachial Artery Reactivity Task Force. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol. 2002 Jan 16;39(2):257-65. doi: 10.1016/s0735-1097(01)01746-6.
PubMed 11788217
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2006. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of The Effect of Vascular Distensibility on Endothelial-Dependent Vasoreactivity in Subjects With Systolic Hypertension Before and After Receiving Oral Alagebrium or Placebo for 8 Weeks (STRETCH)
- ClinicalTrials.gov ID
- NCT00302250
- Acronym / sponsor ID
- ALT-711-0217 (Amended)
- Conditions
- Cardiovascular Disease
- Keywords
- Cardiovascular, Flow-mediated vasodilation (FMD), Pulse perfusion-mediated vasodilation (PPMV), Endothelial function, Heart failure
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants
- Lead sponsor
- Synvista Therapeutics, IncIndustry (pharma, biotech, devices)
- Collaborators
- National Institutes of Health (NIH), National Heart and Lung Institute
- Study start
- Feb 2006
- Study completion
- Dec 2006
- First posted
- 14 Mar 2006 (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 primary objective of the double-blind segment is to compare effects of alagebrium vs placebo on change from baseline in endothelial function, as assessed by flow-mediated vasodilation (FMD).
Detailed description
The secondary objectives of the double-blind segment are to:
- Compare the effects of alagebrium vs placebo on the change from baseline in endothelial-mediated vasoreactivity immediately after exercise, as assessed by pulse perfusion-mediated vasodilation (PPMV).
- Confirm results observed in the single-blind segment.
- Explore several variables as potential independent predictors of vascular stiffness and endothelial function. These parameters include age, body mass index, gender, renal disease, history of cardiovascular disease, serum cholesterol, and antihypertensive medication use.
- Provide insight into nitric oxide-dependent endothelial function in the setting of increased arterial stiffness by determination of substances in the nitric oxide signaling pathway (specifically, levels of serum cGMP; serum nitrate and nitrite; and serum asymmetric dimethylarginine [ADMA], an endogenous inhibitor of nitric oxide synthase).
- Provide insight into the relationship between AGE levels (AGE markers: pentosidine, furosine), collagen metabolism (collagen markers: procollagen I carboxyterminal propeptide [PICP], procollagen type I N terminal propeptide [PINP], cross-linked carboxyterminal telopeptide of Type I collagen [ICTP], n-terminal propeptide of type III procollagen [PIIINP]), and endothelial function; and insight into the changes in these markers in response to treatment with an AGE cross-link breaker (alagebrium).
- Provide insight into the relationship between markers of inflammation [specifically, free and total serum matrix metalloproteinase-1(MMP-1), free tissue inhibitor of metalloproteinase 1 (TIMP1), intercellular adhesion molecule-1 (ICAM), vascular cellular adhesion molecule (VCAM), P-selectin, von Willebrand factor (vWf), interleukin-6 (IL-6), endothelin 1, VEGF, NFkβ, TGF-β, IGF-1 and high-sensitivity C reactive protein (hs CRP)] and endothelial function; and insight into the changes in these markers in response to treatment with an AGE cross-link breaker (alagebrium).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female 50 years of age or greater.
- Diagnosed with systolic hypertension (systolic blood pressure >140 mm Hg and (less than or equal to) 200 mm Hg, and a diastolic blood pressure (less than or equal to) 95 mm Hg) and elevated pulse pressure (systolic blood pressure [SBP] minus diastolic blood pressure [DBP] greater than 60 mm Hg).
- Normal left ventricular function (ejection fraction > 55%) at baseline (Visit 3).
- Brachial artery must be able to be visualized for FMD and PPMV determinations.
- Able to perform bicycle exercise.
Key exclusion criteria (12 listed)
- Aortic stenosis, prior known coronary artery disease (including myocardial infarction), cerebrovascular accident, or peripheral vascular disease.
- Uncontrolled hypertension (SBP > 200/DBP > 95 mm Hg).
- Atrial fibrillation, diabetes mellitus treated with insulin, or chronic lung disease.
- Any additional condition(s) which, in the opinion of the investigator, would prohibit the subject from completing the study, or not be in the best interest of the subject.
- Treatment with nitrates, or a change in antihypertensive medications within the last 1 month.
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 |
|---|---|---|
| ALT-711 (alagebrium chloride) | Drug | – |
Primary outcome
Not reported in the source record.
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 22 Mar 2006.
- Background: PubMed 15812746Little WC, Zile MR, Kitzman DW, Hundley WG, O'Brien TX, Degroof RC. The effect of alagebrium chloride (ALT-711), a novel glucose cross-link breaker, in the treatment of elderly patients with diastolic heart failure. J Card Fail. 2005 Apr;11(3):191-5. doi: 10.1016/j.cardfail.2004.09.010.
- Background: PubMed 11571237Kass DA, Shapiro EP, Kawaguchi M, Capriotti AR, Scuteri A, deGroof RC, Lakatta EG. Improved arterial compliance by a novel advanced glycation end-product crosslink breaker. Circulation. 2001 Sep 25;104(13):1464-70. doi: 10.1161/hc3801.097806.
- Background: PubMed 2759675Liu ZR, Ting CT, Zhu SX, Yin FC. Aortic compliance in human hypertension. Hypertension. 1989 Aug;14(2):129-36. doi: 10.1161/01.hyp.14.2.129.
- Background: PubMed 11788217Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, Herrington D, Vallance P, Vita J, Vogel R; International Brachial Artery Reactivity Task Force. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol. 2002 Jan 16;39(2):257-65. doi: 10.1016/s0735-1097(01)01746-6.
- Related InfoLink provided by the sponsor.
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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.
Susan Zieman, MD, PhD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ALT-711 (alagebrium chloride) in people with Cardiovascular Disease, run by Synvista Therapeutics, Inc 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 7 inclusion and 12 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 22 Mar 2006. 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 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 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00302250, which also lists 4 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 22 Mar 2006.