- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT00787059
AC6 Gene Transfer for CHF
6. februar 2018 opdateret af: Hammond, H. Kirk, M.D.
Phase I/II Study AC6 Gene Transfer for Congestive Heart Failure
This research study is designed to determine: 1) whether gene transfer using an agent called Ad5.hAC6 (adenovirus-5 encoding human adenylyl cyclase type 6) can be given safely to patients with congestive heart failure (CHF) and 2) whether this agent may be of benefit in heart failure.
Gene transfer is a process by which genes are introduced into cells and the cells then produce the specific protein that the gene directs, in this case, a protein known as adenylyl cyclase type 6 (AC6).
The gene is carried into the heart cells by a modified virus.
The virus that is modified is an adenovirus (Ad5), a virus that sometimes causes a brief cold.
In extensive animal experiments, it was found that increased amounts of AC6 protein in heart cells appeared to make the heart pump more vigorously.
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
This research study is designed to determine: 1) whether gene transfer using an agent called Ad5.hAC6 (adenovirus-5 encoding human adenylyl cyclase type 6) can be given safely to patients with congestive heart failure (CHF) and 2) whether this agent may be of benefit in heart failure.
Gene transfer is a process by which genes are introduced into cells and the cells then produce the specific protein that the gene directs, in this case, a protein known as adenylyl cyclase type 6 (AC6).
The gene is carried into the heart cells by a modified virus.
The virus that is modified is an adenovirus (Ad5), a virus that sometimes causes a brief cold.
In extensive animal experiments, it was found that increased amounts of AC6 protein in heart cells appear to make the heart pump more vigorously.
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
56
Fase
- Fase 2
- Fase 1
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
-
-
California
-
San Diego, California, Forenede Stater, 92161
- VA San Diego Healthcare System
-
San Diego, California, Forenede Stater, 92037
- University of California, San Diego
-
-
Illinois
-
Chicago, Illinois, Forenede Stater, 60611
- Northwestern University Feinberg School of Medicine
-
-
Minnesota
-
Minneapolis, Minnesota, Forenede Stater, 55407
- Minneapolis Heart Institute Foundation
-
-
Utah
-
Salt Lake City, Utah, Forenede Stater, 84132
- University of Utah Health Care, Utah
-
-
Vermont
-
Burlington, Vermont, Forenede Stater, 05401
- Fletcher Allen Health Care
-
-
Wisconsin
-
Madison, Wisconsin, Forenede Stater, 53792
- University of Wisconsin-Madison
-
-
Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år til 80 år (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
Inclusion Criteria
- Male or non-pregnant female patients aged 18-80 years of age
- ≥3-month history of heart failure
- Compensated (stable) CHF not on intravenous inotropes, vasodilators or diuretics, on optimal medical and device therapy as defined by AHA/ACC Guidelines
- LV ejection fraction (on optimal therapy) no greater than 40%
- Implanted cardiac defibrillator
- At least one major coronary artery (or graft) with <50% proximal obstruction
- Patients unable to walk (spinal injury, orthopedic problems) can be enrolled if all other criteria are met.
- Women of child-bearing capacity must have a negative pregnancy test within 2 days of test substance administration, and female and male patients must be willing to use birth control during sex for 12w after test substance administration if the female partner is of child-bearing capacity.
- Subjects willingly provide informed consent consistent with ICH-GCP guidelines
Exclusion Criteria
- Unstable or Class IV angina
- Coronary revascularization planned or predicted in next 6 months
- Ischemic myocardium in 3 or more regions of a single perfusion bed, as assessed by stress echocardiography or jeopardized viable myocardium >15% on perfusion imaging.
- ≥50% occlusion of an "unprotected" left main coronary artery. If arterial or venous conduits provide blood flow to the distal left coronary circulation (ie, patent bypass grafts) then left main disease is "protected" and such patients are not excluded. The cardiologist performing the cardiac catheterization will make these decisions.
- 2° AV Block (Mobitz 2) or 3° AV block unless pacemaker is present
- Hospitalization for CHF requiring intravenous inotropes or vasodilators in the past 4 weeks
- History of biopsy proven myocarditis
- Myocardial infarction in previous 6 months
- Restrictive, hypertrophic or infiltrative cardiomyopathy or chronic pericarditis
- Previous or planned organ transplant recipient or donor.
- Thrombocytopenia (<100,000 platelets/µl) or bleeding diathesis
- COPD requiring supplemental oxygen at home
- AST > 2 times upper limit of normal or chronic liver disease such as cirrhosis or Hepatitis C Virus (HCV). Patients with HCV are eligible only if both of two conditions are met: a) liver function tests are normal; AND b) liver biopsy is normal or shows only mild fibrosis.
- Current or predicted hemodialysis within 12 months or estimated glomerular filtration rate (EGFR) <30 ml/min. On online EGFR calculator that uses sex, age, body weight and serum creatinine is available at: www.kidney.org/professionals/kdoqi/gfr_calculator.cfm. Use the higher of two EGFR results, which are based upon MDRD and CKD-EPI formulas.
- CVA or TIA <6 months prior to enrollment
- Patients who are immunosuppressed by medicines (corticosteroids, methotrexate, cyclophosphamide, cyclosporine), illnesses (AIDS, HIV), or neutrophil count <1000/mm3
- Patients receiving other investigational drug therapy within 30 days of enrollment including gene transfer
- Patients with diseases other than CHF that, in the opinion of the investigator, put the subject at risk or adversely affect the results
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Firedobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: Ad5.hAC6
Will receive intracoronary adenovirus encoding human adenylyl cyclase type 6
|
Intracoronary delivery of test substance in 3:1 randomization (Ad5.hAC6
: placebo) with dose escalation, starting at 3.2 x 10^9 vp to 10^12 vp in 5 dose groups
|
|
Placebo komparator: sucrose solution
Will receive intracoronary sucrose solution
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Combined: a) Exercise treadmill time; b) LV function by echocardiography before and during dobutamine infusion; c) Rate of LV pressure development and decline (dP/dt and -dP/dt) before and during dobutamine infusion.
Tidsramme: Before, 4w, 12w
|
Before, 4w, 12w
|
Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Symptoms (KCCQ); hemodynamics; ICD discharge frequency
Tidsramme: Before, 4w, 12 w
|
Before, 4w, 12 w
|
Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Efterforskere
- Studieleder: H. Kirk Hammond, MD, UCSD; VA San Diego Healthcare System; Veterans Medical Research Foundation
- Ledende efterforsker: William Penny, MD, UCSD; VA San Diego Healthcare System; Veteran's Medical Research Foundation
- Ledende efterforsker: Jay H Traverse, MD, Minneapolis Heart Institute Foundation
- Ledende efterforsker: Clyde W Yancy, MD, Bluhm Cardiovascular Institute, Northwestern Memorial Hospital
- Ledende efterforsker: Matthew W Watkins, MD, Fletcher Allen Health Care, University of Vermont
- Ledende efterforsker: Eric D Adler, MD, University of California, San Diego
- Ledende efterforsker: David R Murray, MD, University of Wisconsin, Madison
- Ledende efterforsker: Amit Patel, MD, University of Utah Health Care, Utah
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart
1. juli 2010
Primær færdiggørelse (Faktiske)
1. januar 2015
Studieafslutning (Faktiske)
16. november 2017
Datoer for studieregistrering
Først indsendt
6. november 2008
Først indsendt, der opfyldte QC-kriterier
6. november 2008
Først opslået (Skøn)
7. november 2008
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
9. februar 2018
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
6. februar 2018
Sidst verificeret
1. august 2017
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- 365
- P01HL066941 (U.S. NIH-bevilling/kontrakt)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
UBESLUTET
IPD-planbeskrivelse
The trial remains blinded
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .