Condition category
Circulatory System
Date applied
06/06/2006
Date assigned
16/06/2006
Last edited
30/09/2008
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Michael Ward

ORCID ID

Contact details

30 Bond Street
8th floor Queen wing
Toronto
M5B 1W8
Canada
+1 416 864 5733
wardm@smh.toronto.on.ca

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

CT-PAH 001

Study information

Scientific title

Acronym

The PHACeT trial

Study hypothesis

The primary objective of this phase I clinical trial is to establish the safety of autologous progenitor cell-based gene delivery of human nitric oxide synthase (heNOS) in patients with severe symptomatic pulmonary arterial hypertension (PAH) refractory to conventional treatment.

Please note that, as of 24/09/2008, the anticipated end date of this trial has been updated from 08/05/2008 to 31/10/2009.

Ethics approval

This study was approved by the Research Ethics Board (REB) of St. Michael's Hospital in May 2006 (ref: REB 04-253)

Study design

Phase I, open-label, non-randomised, dose-escalation trial. Doses are assigned sequentially.

Primary study design

Interventional

Secondary study design

Non randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

Idiopathic pulmonary arterial hypertension

Intervention

A total of 18 patients will be studied using an open-label, dose-escalating protocol; three patients will be entered into each of the five dosing panels. An additional three patients will be entered into the final dose panel to establish safety at the maximum tolerated dose.

Apheresis is performed to obtain mononuclear cells from the patientsÂ’ blood. These cells will then be engineered with human nitric oxide synthase (heNOS) and returned back to the patient (autologous) via the right ventricular port of a pulmonary arterial line in divided doses over a three-day elective hospitalisation. Follow-up hemodynamic measures are recorded at three months post-cell delivery.

Intervention type

Drug

Phase

Phase I

Drug names

Nitric oxide

Primary outcome measures

1. Tolerability and safety of the injection of genetically engineered progenitor cells in patients with severe PAH
2. Clinically significant changes in hemodynamic parameters
3. Time to clinical worsening
4. Contrast echo assessment of pulmonary arterial-venous shunting
5. Pulmonary function with diffusing capacity of the lung for carbon monoxide (DLCO)
6. Changes in ventilation perfusion scan
7. Dypnea by Borg index
8. Immune surveillance
9. Human nitric oxide synthase (heNOS) plasmid detection in systemic arterial blood pre- and post-cell delivery

Secondary outcome measures

Potential efficacy of this approach will be assessed by changes in hemodynamic pressures, patient perceived quality of life and exercise capacity.

Overall trial start date

08/05/2006

Overall trial end date

31/10/2009

Reason abandoned

Eligibility

Participant inclusion criteria

1. Age >=18 years and <=80 years
2. Clinical diagnosis of idiopathic PAH
3. Familial PAH or anorexigen-induced PAH
4. Specified 6-minute walk distance

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

18

Participant exclusion criteria

1. Intra or extra cardiac communication between the right- and left-sided circulations
2. Hemodynamic instability
3. Left ventricular ejection fraction <=40%
4. Thromboembolic event or recent hospitalisation for worsening right-sided heart failure in last three months
5. Central venous pressure (CVP) >20 mmHg at time of research heart catheterisation
6. Pregnancy
7. Concurrent hepatitis or HIV

Recruitment start date

08/05/2006

Recruitment end date

31/10/2009

Locations

Countries of recruitment

Canada

Trial participating centre

30 Bond Street
Toronto
M5B 1W8
Canada

Sponsor information

Organisation

Northern Therapeutics Inc (Canada)

Sponsor details

c/o Dr Duncan Stewart
725 Parkdale Avenue
Ottawa
Ontario
K1Y 4E9
Canada
+1 613 761 5341
djstewart@ohri.ca

Sponsor type

Industry

Website

http://www.northernther.com

Funders

Funder type

Industry

Funder name

Northern Therapeutics Inc (Canada)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes