EmphysemaNCT03673176
Lung Volume Reduction for Severe Emphysema by Stereotactic Ablative Radiation Therapy
A study testing Stereotactic Ablative Radiotherapy (SABR) in people with Emphysema, run by Stanford University at 1 site in United States.
Trial summary
Since medical therapies offer only modest palliation and minimal hopes for improved survival to COPD patients, surgical therapies have been designed that may provide greater benefits in selected patients. Lung transplantation, for example, clearly improves survival and quality of life in patients with end stage COPD. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Emphysema
- What is being tested?
- Stereotactic Ablative Radiotherapy (SABR)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Feb 2013to 2 Aug 2021
- Phase
- Interventional
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pulmonary Function:
- Severe COPD with severe reduction in quality of life due to dyspnea
- Moderate to Severe emphysematous destruction of lung parenchyma on chest CT
- FEV1 < 45% predicted and >18% predicted
- FEV1/FVC < .7
- DLCO > 18% predicted
Show all 12Show fewer
- Residual Volume > 160% predicted (by plethysmography)
- Arterial Blood Gas:
- paO2>40 on room air at rest
- paCO2<55
- General:
- Successful completion of 16 sessions of pulmonary rehabilitation
Who cannot join
- Predominate chronic bronchitis (none or mild emphysematous destruction of lung on chest CT).
- Pulmonary function tests / lung volumes that do not meet above criteria.
- Active coronary ischemia (stress test required if clinical symptoms).
- Inability to complete 16 sessions of pulmonary rehabilitation.
- Pregnancy.
- Presence of lung cancer.
Trial locations and contacts
1 site in 1 country.
About this study
Since medical therapies offer only modest palliation and minimal hopes for improved survival to COPD patients, surgical therapies have been designed that may provide greater benefits in selected patients. Lung transplantation, for example, clearly improves survival and quality of life in patients with end stage COPD. This comes at substantial economic cost, however, as well as the at the cost of complications that may result from the complex surgery and from life-long immunosuppression. In addition, nearly all lung transplants will fail within 5 years as a result of progressive bronchiolitis obliterans, which we currently have no way to prevent or treat.
A second operation designed to treat severe COPD patients is lung volume reduction surgery (LVRS). This operation, designed for patients with predominant emphysema rather than chronic bronchitis, is among the most carefully studied operations ever developed.
We believe that by reducing the volume of emphysematous lung with the precise target localization made possible by image-guided SABR, that we will be able to duplicate the benefits of surgical lung volume reduction with far less risk. We believe that this may represent a major advance in the therapy of emphysema - a highly prevalent disease. It may provide not only palliation but also increased survival, as does surgical lung volume reduction, in carefully selected patients.
Read the detailed description
Stereotactic Ablative Radiotherapy (SABR), also called stereotactic body radiation therapy (SBRT), is a relatively recent advance in radiotherapy which allows high doses of radiation to be transmitted to focused areas (typically malignancies), allowing higher rates of tumoricidal activity, generally lower complications, and greater convenience for patients since it can be delivered in 1 to just a few sessions. As the radiation is administered from multiple directions according to stereotactic planning, high doses can be delivered to the tissues with rapid fall-off to relatively low doses in even nearby, surrounding normal tissues. This technique was initially applied to brain tumors- an application which over the years has met with great success. More recently, it has been applied with substantial success and is gaining increasing acceptance as a primary mode of therapy for stage I lung malignancies, and malignancies in multiple other body areas.
In the lung, the rate of pneumonitis resulting from SABR is far lower than the rates incurred by conventional external beam radiotherapy. In conventional external beam radiotherapy reported pneumonitis rates range from 13-37% (7), depending on dose and field size. Reported rates of symptomatic pneumonitis after lung SABR are significantly lower and generally are ~5% (8). SABR does, however, typically leave a scar in the area of lung that has been treated (9). Importantly, there appears to be contraction of surrounding lung parenchyma into this scar resulting in an effect that is essentially a "lung volume reduction." One often sees clear loss of lung volume following any form of lung radiotherapy. With SABR, this "volume reduction" is achieved with a far lower risk of morbidity - in particular, less risk of pneumonitis.
- Conditions
- Emphysema
- Being tested
- Stereotactic Ablative Radiotherapy (SABR)
- Medical subject headings
- Emphysema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stereotactic Ablative Radiotherapy (SABR)Radiation
The prescribed dose will be 45 Gy in three fractions of 15 Gy, on each side that is treated.
| Study group | Role | What they receive |
|---|---|---|
| Stereotactic Ablative Radiotherapy | Experimental | Experimental stereotactic ablative radiation treatment Receives: Radiation: Stereotactic Ablative Radiotherapy (SABR) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Count of Patients With Grade 3 or Higher Adverse Events.
Adverse events will be based upon National Cancer Institute Common Terminology Criteria
Measured: 18 months
Secondary outcomes (8)
Change From Baseline Value in Forced Expiratory Volume Percent Predicted
Forced Expiratory Volume will be taken both prior (baseline) and following the procedure (months 6, 12, and 18)
Measured: Baseline and months 6, 12, and 18
Change From Baseline Value in Forced Expiratory Volume in 1 Second (Liters)
Forced Expiratory Volume will be taken both prior (baseline) and following the procedure (months 6, 12, and 18)
Measured: Baseline and months 6, 12, and 18
Change From Baseline in Diffusing Capacity for Carbon Dioxide (% Predicted)
Diffusing Capacity for Carbon Dioxide will be taken both prior (baseline) and following the procedure (months 6, 12, and 18)
Measured: Baseline and months 6, 12, and 18
Change From Baseline in 6 Minute Walk Test (Meters)
The walk test will be done both prior (baseline) and following the procedure (month 6)
Measured: Baseline and month 6
Total Lung Capacity (% of Predicted Value)
Total Lung Capacity will be measured both prior (baseline) and following the procedure (up to 18 months)
Measured: Baseline and date of last available time-point in follow-up period (up to 18 months)
Residual Volume (RV) (% of Predicted Value)
Residual volume (RV) is the volume of air remaining in the lungs after maximum forceful expiration. In other words, it is the volume of air that cannot be expelled from the lungs, thus causing the alveoli to remain open at all times.
Measured: Baseline and date of last available time-point in follow-up period (up to 18 months)
Short Form (SF)-36 Quality of Life Survey Score
The SF-36 Physical Component Summary (PCS) assesses limitations in physical functioning due to health problems, limitations in usual role because of physical health problems, bodily pain, and general health perceptions; the mental component summary (MCS) assesses vitality, limitations in social functioning because of physical or emotional problems, limitations in usual role due to emotional problems, and general mental health. The PCS and MCS scores each range from 0 (worst) to 100 (best). Increases from baseline indicate improvement.
Measured: Baseline and months 6
Modified Borg Dyspnea Scale
This is a patient-reported scale to rate the difficulty of breathing. The scale ranges from 0 to 10, wherein "0" indicates no difficulty breathing, and "10" indicates a maximal difficulty in breathing. Patients may report in whole numbers, from 0 to 10, in addition to reporting 0.5, which indicates "very, very slight (just noticeable) difficulty in breathing."
A negative change in score indicates a reduction in patient-reported breathing difficulty. The greater the negative change, the better the patient-reported breathing.
Measured: Baseline and months 6, 12, and 18
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2018
- Study start11 Feb 2013
- Primary completion2 Aug 2021
- Study completion2 Aug 2021
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 EmphysemaStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- Varian, a Siemens Healthineers Company
- Responsible party
- Principal investigator, Joseph B. Shrager, MD, Stanford University
- Investigators
- Joseph B Shrager, M.D, Study director, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03673176
- Sponsor's protocol ID
- e-protocol 23203
- Status last verified
- Jun 2024
- First submitted
- 20 Nov 2017
- Last updated
- 11 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Kamtam DN, Binkley MS, Kapula N, Sadeghi C, Nesbit S, Guo HH, Chang J, Maxim PG, Diehn M, Loo BW Jr, Shrager JB. First in Human Phase 1 Clinical Trial of Stereotactic Irradiation to Achieve Lung Volume Reduction (SILVR) in Severe Emphysema. Int J Radiat Oncol Biol Phys. 2024 Oct 1;120(2):345-356. doi: 10.1016/j.ijrobp.2024.03.049. Epub 2024 Apr 12.
PubMed 38615887
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lung Volume Reduction for Severe Emphysema by Stereotactic Ablative Radiation Therapy
- ClinicalTrials.gov ID
- NCT03673176
- Acronym / sponsor ID
- e-protocol 23203
- Conditions
- Emphysema
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- Varian, a Siemens Healthineers Company
- Study start
- 11 Feb 2013 (actual)
- Primary completion
- 2 Aug 2021 (actual)
- Study completion
- 2 Aug 2021 (actual)
- First posted
- 17 Sep 2018 (actual)
- Results
- Posted 11 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Since medical therapies offer only modest palliation and minimal hopes for improved survival to COPD patients, surgical therapies have been designed that may provide greater benefits in selected patients. Lung transplantation, for example, clearly improves survival and quality of life in patients with end stage COPD. This comes at substantial economic cost, however, as well as the at the cost of complications that may result from the complex surgery and from life-long immunosuppression. In addition, nearly all lung transplants will fail within 5 years as a result of progressive bronchiolitis obliterans, which we currently have no way to prevent or treat.
A second operation designed to treat severe COPD patients is lung volume reduction surgery (LVRS). This operation, designed for patients with predominant emphysema rather than chronic bronchitis, is among the most carefully studied operations ever developed.
We believe that by reducing the volume of emphysematous lung with the precise target localization made possible by image-guided SABR, that we will be able to duplicate the benefits of surgical lung volume reduction with far less risk. We believe that this may represent a major advance in the therapy of emphysema - a highly prevalent disease. It may provide not only palliation but also increased survival, as does surgical lung volume reduction, in carefully selected patients.
Detailed description
Stereotactic Ablative Radiotherapy (SABR), also called stereotactic body radiation therapy (SBRT), is a relatively recent advance in radiotherapy which allows high doses of radiation to be transmitted to focused areas (typically malignancies), allowing higher rates of tumoricidal activity, generally lower complications, and greater convenience for patients since it can be delivered in 1 to just a few sessions. As the radiation is administered from multiple directions according to stereotactic planning, high doses can be delivered to the tissues with rapid fall-off to relatively low doses in even nearby, surrounding normal tissues. This technique was initially applied to brain tumors- an application which over the years has met with great success. More recently, it has been applied with substantial success and is gaining increasing acceptance as a primary mode of therapy for stage I lung malignancies, and malignancies in multiple other body areas.
In the lung, the rate of pneumonitis resulting from SABR is far lower than the rates incurred by conventional external beam radiotherapy. In conventional external beam radiotherapy reported pneumonitis rates range from 13-37% (7), depending on dose and field size. Reported rates of symptomatic pneumonitis after lung SABR are significantly lower and generally are ~5% (8). SABR does, however, typically leave a scar in the area of lung that has been treated (9). Importantly, there appears to be contraction of surrounding lung parenchyma into this scar resulting in an effect that is essentially a "lung volume reduction." One often sees clear loss of lung volume following any form of lung radiotherapy. With SABR, this "volume reduction" is achieved with a far lower risk of morbidity - in particular, less risk of pneumonitis.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Stereotactic Ablative Radiotherapy | Experimental | Radiation: Stereotactic Ablative Radiotherapy (SABR)Experimental stereotactic ablative radiation treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Severe COPD with severe reduction in quality of life due to dyspnea
- Moderate to Severe emphysematous destruction of lung parenchyma on chest CT
- paO2>40 on room air at rest
- paCO2<55
- Successful completion of 16 sessions of pulmonary rehabilitation
Key exclusion criteria (6 listed)
- Predominate chronic bronchitis (none or mild emphysematous destruction of lung on chest CT).
- Pulmonary function tests / lung volumes that do not meet above criteria.
- Active coronary ischemia (stress test required if clinical symptoms).
- Inability to complete 16 sessions of pulmonary rehabilitation.
- Pregnancy.
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 |
|---|---|---|
| Stereotactic Ablative Radiotherapy (SABR)The prescribed dose will be 45 Gy in three fractions of 15 Gy, on each side that is treated. | Radiation | Stereotactic Ablative Radiotherapy |
Primary outcome
Count of Patients With Grade 3 or Higher Adverse Events.
Time frame: 18 months
Adverse events will be based upon National Cancer Institute Common Terminology Criteria
8 secondary outcomes
Change From Baseline Value in Forced Expiratory Volume Percent Predicted
Time frame: Baseline and months 6, 12, and 18
Change From Baseline Value in Forced Expiratory Volume in 1 Second (Liters)
Time frame: Baseline and months 6, 12, and 18
Change From Baseline in Diffusing Capacity for Carbon Dioxide (% Predicted)
Time frame: Baseline and months 6, 12, and 18
Change From Baseline in 6 Minute Walk Test (Meters)
Time frame: Baseline and month 6
Total Lung Capacity (% of Predicted Value)
Time frame: Baseline and date of last available time-point in follow-up period (up to 18 months)
Residual Volume (RV) (% of Predicted Value)
Time frame: Baseline and date of last available time-point in follow-up period (up to 18 months)
Short Form (SF)-36 Quality of Life Survey Score
Time frame: Baseline and months 6
Modified Borg Dyspnea Scale
Time frame: Baseline and months 6, 12, and 18
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 38615887Kamtam DN, Binkley MS, Kapula N, Sadeghi C, Nesbit S, Guo HH, Chang J, Maxim PG, Diehn M, Loo BW Jr, Shrager JB. First in Human Phase 1 Clinical Trial of Stereotactic Irradiation to Achieve Lung Volume Reduction (SILVR) in Severe Emphysema. Int J Radiat Oncol Biol Phys. 2024 Oct 1;120(2):345-356. doi: 10.1016/j.ijrobp.2024.03.049. Epub 2024 Apr 12.
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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.
Joseph B Shrager, M.D study director
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Stereotactic Ablative Radiotherapy (SABR) in people with Emphysema, run by Stanford University 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 12 inclusion and 6 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 11 Jul 2024. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jul 2024). 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?
Count of Patients With Grade 3 or Higher Adverse Events. (time frame: 18 months). 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 NCT03673176, 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 11 Jul 2024; AzTrials last refreshed its copy on 1 Nov 2026.