EndocardialVascularEndothelialGrowth Factor D(VEGF-D)Gene Therapy for the Treatment of Severe Coronary Heart Disease

NCT01002430 | Completed Phase 1

• 1 other identifier: KUH5101035
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to evaluate the safety and efficacy of catheter mediated endocardial adenovirus VEGF-D gene therapy in patients with severe coronary heart disease.

Conditions

Angina Pectoris; Myocardial Infarction

Keywords

Myocardial ischemia; Refractory angina pectoris; Vascular endothelial growth factor; Gene therapy; Perfusion

Outcome Measures

Primary Outcomes (1)

• Assessments for safety and tolerability as measured as the acute and late adverse effects, laboratory parameters, biodistribution of the vector, anti-adenovirus antibodies and VEGF-levels before and in several time points after the gene transfer.

  1 year

Secondary Outcomes (3)

• Efficacy of GT to increase myocardial perfusion in MRI and PET.

  1 year

• Functional capacity in exercise test, LV-function in echocardiography, arrhythmias in 24-hours Holter-recording will be analyzed.

  1 year

• Improvement in symptoms, QOL and medication.

  1 year

Study Arms (2)

Gene therapy

EXPERIMENTAL

Biological: VEGF-D gene transfer

Control

NO INTERVENTION

Control patients will have electroanatomic mapping procedure but no gene injections.

Interventions

VEGF-D gene transfer BIOLOGICAL

Gene transfer will be performed by using endocardial injection system (NOGATM) and an escalating dose of 1x109, 1x1010 and 1x1011 vpu of AdVEGF-D will be injected into 10 sites of the myocardium (0.2 ml per site).

Gene therapy

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• informed consent signed,
• age between 30 and 80 years,
• significant angina pectoris (CCS II-III) despite of maximal medication,
• significant stenosis in coronary angiography (stenosis \> 60 %),
• contraindication to coronary angioplasty or by pass operation (diffuse or distal stenosis,
• chronic total occlusion,
• vessels with difficult anatomy,
• stenosis with severe calcifications,
• stenosis in small vessels (\< 2.5 mm)),
• reversible myocardial perfusion defects detected by pharmacological adenosine or dobutamine assisted perfusion MRI,
• angina pectoris or ischemic ST-depression (\> 1 mm) in the exercise test,
• left ventricle wall \> 8 mm detected by transthoracal echocardiography (treatment area).

You may not qualify if:

• women in fertile age,
• patients with type 1 diabetes mellitus or severe end-stage type 2 diabetes mellitus,
• diabetic retinopathy,
• atrial fibrillation,
• clinically significant anemia (hemoglobin count \< 120 mg/l in male, \< 110 mg/l in female; hematocrit \< 0.36), leukopenia (b-leukocyte count \< 3.0x109/l), leukocytosis (b-leukocyte count \> 12.0x109/l) or thrombocytopenia (b-thrombocyte count \< 100x109/l), renal insufficiency (s-creatinine \> 160mg/l),
• liver insufficiency (s-alanine amino transferase and s-alcaline phosphatase over 2 x normal),
• haematuria of unknown origin,
• severe hypertension (systolic blood pressure \> 200 mmHg or diastolic blood pressure \> 110 mmHg) or significant hypotension (systolic blood pressure \< 90mmHg),
• significant obesity (BMI \> 35),
• cardiac pacemaker,
• acute infection,
• immunosuppressive medication,
• significant impairment of the left ventricular function (EF \< 25% in TTE or CO \< 2 l in MRI),
• congestive heart failure,
• haemodynamically significant (gradus 3-4/4) aortic regurgitation or other heart disease needing surgery,

Sponsors & Collaborators

• Kuopio University Hospital: lead
• University of Eastern Finland: collaborator

Study Sites (1)

Kuopio University Hospital

Kuopio, Finland

Location

Related Publications (1)

• Leikas AJ, Hassinen I, Kivela A, Hedman A, Mussalo H, Yla-Herttuala S, Hartikainen JEK. Intramyocardial adenoviral vascular endothelial growth factor-D∆N∆C gene therapy does not induce ventricular arrhythmias. J Gene Med. 2022 Aug;24(8):e3437. doi: 10.1002/jgm.3437. Epub 2022 Jul 6.

  PMID: 35750637 DERIVED

MeSH Terms

Conditions

Angina Pectoris; Myocardial Infarction; Myocardial Ischemia

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Infarction; Ischemia; Pathologic Processes; Necrosis

Study Officials

• Juha Hartikainen

  Kuopio University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Director, Heart Center

Study Record Dates

• First Submitted: October 23, 2009
• First Posted: October 27, 2009
• Study Start: January 10, 2010
• Primary Completion: June 15, 2015
• Study Completion: June 15, 2015
• Last Updated: March 8, 2018

Record last verified: 2018-03

Locations

FI (1)