Disk, HerniatedPhase 1NCT01339377
Safety and Effectiveness Study of the AO-1000 Device to Treat Contained Herniated Discs
A Phase 1 study testing AO-1000 in people with Disk, Herniated, run by ActiveO Inc. at 3 sites in Canada.
Trial summary
To evaluate the safety and effectiveness of the AO-1000 device to treat and relieve the pain of symptomatic subjects with contained herniated discs. This single-arm pilot study will be used as a go vs. no-go decision on performing a randomized-controlled trial. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Disk, Herniated
- What is being tested?
- AO-1000
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 3 sitesCanada
- Study dates
- Aug 2011to Apr 2016
- Phase
- Phase 1
- 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 to 70 years of age
- Herniated disc between L1 and S1 evident on diagnostic imaging
- Sciatica with or without lower back pain for > 3 months
- Failure to improve with non-operative care (Conservative treatment failure)
- Sciatica with or without lower back pain exacerbated by sitting and/or standing with recumbent relief
- A preoperative leg or back VAS (pain) score between 40 and 90 mm on a 100 mm scale. (moderate to severe pain)
Show all 9Show fewer
- A preoperative ODI (function) score between 40 and 90 (moderate to severe functional disability)
- Able and willing to return for the follow-up evaluations
- The pain must be consistent with the dermatome pattern and must be clearly identifiable to the herniated disc.
Who cannot join
- Functional neurological deficit evident during neurological exam
- Previous spine surgery in the lumbar region or adjacent to the disc of interest
- Cord compression or cauda equine syndrome
- Structural deformities (e.g. spondylolisthesis, greater than a mild degree of non-discogenic vertebral canal stenosis, greater than a mild degree of scoliosis, spinal fracture, disc herniations > 4 mm, sequestered herniation)
- Extruded/free disc fragment
- Calcified disc fragment
Show all 20Show fewer
- Disc height loss > 75%
- Inaccessible disc due to, for example, overlap of the iliac wings, and/or steep angulation of the L5/S1 disc space
- Coagulopathy evident on blood sample testing
- Platelet count < 50,000
- International Normalized Ratio (INR) > 1.4
- Partial Thromboplastin Time (PTT) > 1.3
- White blood cell count (WBCC) > 12,000
- Infection as evidenced by subject clinical evaluation, history, and blood test
- Any evidence of osteomyelitis/discitis at any level
- Uncontrolled/acute illness
- Women who are pregnant
- Worker's compensation, injury litigation, disability remuneration
- Participation in another clinical investigation or course of care that may confound the outcome of this study
- Smoker
Trial locations and contacts
3 sites in 1 country.
Canada3 sites
University of Western Ontario - London Health Sciences Centre
London, Ontario, N6H 5A5
Toronto Western Hospital
Toronto, Ontario, M5T 2S8
Vancouver General Hospital
Vancouver, British Columbia, V5Z 1M9
About this study
Official title: A Pilot Study to Evaluate the Safety and Effectiveness of Ozone Generated and Injected by the AO-1000 Device in the Treatment of Contained Herniated Discs
To evaluate the safety and effectiveness of the AO-1000 device to treat and relieve the pain of symptomatic subjects with contained herniated discs. This single-arm pilot study will be used as a go vs. no-go decision on performing a randomized-controlled trial.
The study's primary effectiveness objective is to demonstrate that the patient's functionality (based on Oswestry Disability Index scores) has improved from baseline at one month. The study's primary safety objective is to demonstrate that serious device/procedure related adverse events and subsequent surgical interventions are no greater than those in a literature control of other percutaneous disc decompression procedures at discharge, 1 month, 6 months, and 12 months post-treatment.
Secondary objectives are to demonstrate procedural success and improvement in the pain and function of the subjects at 1, 6, and 12 months using the VAS and ODI scales as well as tracking analgesic medication use. Pain and function scores for each follow-up time will be compared to the baseline scores.
Read the detailed description
The AO-1000 device provides an oxygen-ozone treatment for contained herniated discs. An oxygen-ozone treatment is a minimally invasive injection for treating disc herniations that is widely practiced in Europe and Asia. This treatment involves the injection of an oxygen-ozone mixture into the herniated disc and/or the paravertebral muscle surrounding the disc. However, there are no medical ozone generators for this procedure that are currently cleared by the FDA for use in the US. Many studies using a wide range of inclusion/exclusion criteria, ozone concentrations, and procedures have been performed to determine the effectiveness of oxygen-ozone treatment.
A meta-analysis of nearly 8,000 patients from published studies shows a mean improvement of 39 mm for VAS and 25.7 for ODI. The likelihood of complications was 0.064%. Furthermore, no cases of discitis were reported after oxygen-ozone therapy, which is unlike all the other methods of disc volume reduction. This is most likely due to the fact that ozone is a strong oxidizer and an excellent disinfecting agent. The complications shown in the meta-analysis were minor and transient, and easily avoidable by utilizing a device such as the AO-1000 that is designed to eliminate these types of complications (ozone leakage into the treatment room and high ozone concentrations) during this procedure. The estimated complication rate from the meta-analysis is consistent with the Italian Oxygen-Ozone Therapy Federation (FIO) results (no procedure-related adverse events in treatments on 15,000 patients).
The safety of the direct injection of oxygen-ozone gas mixture into the nucleus pulposus was well established in these studies. Therefore, the intent of this study is to obtain data to confirm that a 2 weight percent (wt%) oxygen-ozone mixture delivered from the AO-1000 device is safe and effective for the intended use. This clinical study is designed to bridge the AO-1000 to the extensive prior oxygen-ozone treatment safety and effectiveness data between studies such as those found in the Meta-analysis that did not use the AO-1000 as the delivery system.
- Conditions
- Disk, Herniated
- Being tested
- AO-1000
- Keywords
- Ozone, Oxygen, Oxygen-Ozone, AO-1000, ActiveO, Herniated Disc, Disc, Lumbar
- Medical subject headings
- Intervertebral Disc Displacement
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AO-1000Device
Mixture of 2 weight% ozone in 98 weight% oxygen injected into the nucleus pulposus of a contained herniated disc.
| Study group | Role | What they receive |
|---|---|---|
| AO-1000 Treatment | Experimental | Oxygen-ozone treatment with the AO-1000 device Receives: Device: AO-1000 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Effectiveness Endpoint: Change from Baseline ODI Score at 1 Month
Mean change from baseline ODI score, analyzed at 1 month. The endpoint will be deemed successful if the mean improvement is statistically shown (p<0.05) to be at least 15 points (the minimum detectable change of the ODI).
Measured: 1 month post-treatment
Primary Safety Endpoint: Frequency of Serious Adverse Events Compared to Literature Control
The endpoint will be deemed successful if the number of serious device/procedure related adverse events are statistically shown (p<0.05) to be no greater than those in a literature control of other percutaneous disc decompression procedures.
Measured: 12 months post-treatment
Secondary outcomes (4)
Functional improvement
Mean change from baseline ODI score, analyzed at 6 and 12 months. Each endpoint will be deemed successful if the mean improvement is statistically shown (p<0.05) to be at least 15 points (the minimum detectable change of the ODI).
Measured: 6 and 12 months post-treatment
Leg and Back Pain Improvement
Mean change from separate leg and back pain baseline Visual Analog Scale (VAS) scores, analyzed at 1, 6, and 12 months. Each endpoint (leg VAS and back VAS at each follow-up time) will be deemed successful if the mean improvement is statistically shown (p<0.05) to be at least 20 mm (the minimum clinically important difference of the VAS).
Measured: 1, 6, and 12 months post-treatment
Procedural Success
Technical success, as assessed by successful injection of oxygen-ozone mixture confirmed via CT scan performed immediately following the treatment. A treatment will be considered a success if the CT scan shows gas within the target disc.
Measured: Time of Treatment
Analgesic Medication Use
Change in prescription and over-the-counter (OTC) analgesic medication use, including non-steroidal anti-inflammatory drugs (NSAIDs) from baseline, analyzed at 1, 6, and 12 months. Endpoint will be deemed successful if the number of patients using analgesic medication decreases from baseline.
Measured: 1, 6, and 12 months post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2011 (estimated)
- Study startAug 2011
- Primary completionApr 2016
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Disk, HerniatedStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- ActiveO Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01339377
- Sponsor's protocol ID
- CT2-IPP-001-AO
- Status last verified
- Jul 2016
- First submitted
- 19 Apr 2011
- Last updated
- 15 Jul 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Steppan J, Meaders T, Muto M, Murphy KJ. A metaanalysis of the effectiveness and safety of ozone treatments for herniated lumbar discs. J Vasc Interv Radiol. 2010 Apr;21(4):534-48. doi: 10.1016/j.jvir.2009.12.393. Epub 2010 Feb 25.
PubMed 20188591Pellicanò G, Martinelli F, Tavanti V, et al. The Italian Oxygen-Ozone Therapy Federation (FIO) Study on Oxygen-Ozone Treatment of Herniated Disc. Int J Ozone Ther 6:7-15, 2007.
Oder B, Loewe M, Reisegger M, Lang W, Ilias W, Thurnher SA. CT-guided ozone/steroid therapy for the treatment of degenerative spinal disease--effect of age, gender, disc pathology and multi-segmental changes. Neuroradiology. 2008 Sep;50(9):777-85. doi: 10.1007/s00234-008-0398-2. Epub 2008 May 16.
PubMed 18483728Mixter WJ, Barr JS. Rupture of the intervertebral disc with involvement of the spinal canal. N Engl J Med 211:210-215, 1934.
Andreula CF, Simonetti L, De Santis F, Agati R, Ricci R, Leonardi M. Minimally invasive oxygen-ozone therapy for lumbar disk herniation. AJNR Am J Neuroradiol. 2003 May;24(5):996-1000.
PubMed 12748111Andreula C, Muto M, Leonardi M. Interventional spinal procedures. Eur J Radiol. 2004 May;50(2):112-9. doi: 10.1016/j.ejrad.2003.10.013.
PubMed 15081127Bonetti M, Fontana A, Cotticelli B, Volta GD, Guindani M, Leonardi M. Intraforaminal O(2)-O(3) versus periradicular steroidal infiltrations in lower back pain: randomized controlled study. AJNR Am J Neuroradiol. 2005 May;26(5):996-1000.
PubMed 15891150Gallucci M, Limbucci N, Zugaro L, Barile A, Stavroulis E, Ricci A, Galzio R, Masciocchi C. Sciatica: treatment with intradiscal and intraforaminal injections of steroid and oxygen-ozone versus steroid only. Radiology. 2007 Mar;242(3):907-13. doi: 10.1148/radiol.2423051934. Epub 2007 Jan 5.
PubMed 17209164
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study to Evaluate the Safety and Effectiveness of Ozone Generated and Injected by the AO-1000 Device in the Treatment of Contained Herniated Discs
- ClinicalTrials.gov ID
- NCT01339377
- Acronym / sponsor ID
- CT2-IPP-001-AO
- Conditions
- Disk, Herniated
- Keywords
- Ozone, Oxygen, Oxygen-Ozone, AO-1000, ActiveO, Herniated Disc, Disc, Lumbar
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- ActiveO Inc.Industry (pharma, biotech, devices)
- Study start
- Aug 2011
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 20 Apr 2011 (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.
To evaluate the safety and effectiveness of the AO-1000 device to treat and relieve the pain of symptomatic subjects with contained herniated discs. This single-arm pilot study will be used as a go vs. no-go decision on performing a randomized-controlled trial.
The study's primary effectiveness objective is to demonstrate that the patient's functionality (based on Oswestry Disability Index scores) has improved from baseline at one month. The study's primary safety objective is to demonstrate that serious device/procedure related adverse events and subsequent surgical interventions are no greater than those in a literature control of other percutaneous disc decompression procedures at discharge, 1 month, 6 months, and 12 months post-treatment.
Secondary objectives are to demonstrate procedural success and improvement in the pain and function of the subjects at 1, 6, and 12 months using the VAS and ODI scales as well as tracking analgesic medication use. Pain and function scores for each follow-up time will be compared to the baseline scores.
Detailed description
The AO-1000 device provides an oxygen-ozone treatment for contained herniated discs. An oxygen-ozone treatment is a minimally invasive injection for treating disc herniations that is widely practiced in Europe and Asia. This treatment involves the injection of an oxygen-ozone mixture into the herniated disc and/or the paravertebral muscle surrounding the disc. However, there are no medical ozone generators for this procedure that are currently cleared by the FDA for use in the US. Many studies using a wide range of inclusion/exclusion criteria, ozone concentrations, and procedures have been performed to determine the effectiveness of oxygen-ozone treatment.
A meta-analysis of nearly 8,000 patients from published studies shows a mean improvement of 39 mm for VAS and 25.7 for ODI. The likelihood of complications was 0.064%. Furthermore, no cases of discitis were reported after oxygen-ozone therapy, which is unlike all the other methods of disc volume reduction. This is most likely due to the fact that ozone is a strong oxidizer and an excellent disinfecting agent. The complications shown in the meta-analysis were minor and transient, and easily avoidable by utilizing a device such as the AO-1000 that is designed to eliminate these types of complications (ozone leakage into the treatment room and high ozone concentrations) during this procedure. The estimated complication rate from the meta-analysis is consistent with the Italian Oxygen-Ozone Therapy Federation (FIO) results (no procedure-related adverse events in treatments on 15,000 patients).
The safety of the direct injection of oxygen-ozone gas mixture into the nucleus pulposus was well established in these studies. Therefore, the intent of this study is to obtain data to confirm that a 2 weight percent (wt%) oxygen-ozone mixture delivered from the AO-1000 device is safe and effective for the intended use. This clinical study is designed to bridge the AO-1000 to the extensive prior oxygen-ozone treatment safety and effectiveness data between studies such as those found in the Meta-analysis that did not use the AO-1000 as the delivery system.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AO-1000 Treatment | Experimental | Device: AO-1000Oxygen-ozone treatment with the AO-1000 device |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 18 to 70 years of age
- Herniated disc between L1 and S1 evident on diagnostic imaging
- Sciatica with or without lower back pain for > 3 months
- Failure to improve with non-operative care (Conservative treatment failure)
- Sciatica with or without lower back pain exacerbated by sitting and/or standing with recumbent relief
Key exclusion criteria (20 listed)
- Functional neurological deficit evident during neurological exam
- Previous spine surgery in the lumbar region or adjacent to the disc of interest
- Cord compression or cauda equine syndrome
- Structural deformities (e.g. spondylolisthesis, greater than a mild degree of non-discogenic vertebral canal stenosis, greater than a mild degree of scoliosis, spinal fracture, disc herniations > 4 mm, sequestered herniation)
- Extruded/free disc fragment
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 |
|---|---|---|
| AO-1000Mixture of 2 weight% ozone in 98 weight% oxygen injected into the nucleus pulposus of a contained herniated disc. | Device | AO-1000 Treatment |
Primary outcome
Primary Effectiveness Endpoint: Change from Baseline ODI Score at 1 Month
Time frame: 1 month post-treatment
Mean change from baseline ODI score, analyzed at 1 month. The endpoint will be deemed successful if the mean improvement is statistically shown (p<0.05) to be at least 15 points (the minimum detectable change of the ODI).
Primary Safety Endpoint: Frequency of Serious Adverse Events Compared to Literature Control
Time frame: 12 months post-treatment
The endpoint will be deemed successful if the number of serious device/procedure related adverse events are statistically shown (p<0.05) to be no greater than those in a literature control of other percutaneous disc decompression procedures.
4 secondary outcomes
Functional improvement
Time frame: 6 and 12 months post-treatment
Leg and Back Pain Improvement
Time frame: 1, 6, and 12 months post-treatment
Procedural Success
Time frame: Time of Treatment
Analgesic Medication Use
Time frame: 1, 6, and 12 months post-treatment
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 15 Jul 2016.
- Background: PubMed 20188591Steppan J, Meaders T, Muto M, Murphy KJ. A metaanalysis of the effectiveness and safety of ozone treatments for herniated lumbar discs. J Vasc Interv Radiol. 2010 Apr;21(4):534-48. doi: 10.1016/j.jvir.2009.12.393. Epub 2010 Feb 25.
- BackgroundPellicanò G, Martinelli F, Tavanti V, et al. The Italian Oxygen-Ozone Therapy Federation (FIO) Study on Oxygen-Ozone Treatment of Herniated Disc. Int J Ozone Ther 6:7-15, 2007.
- Background: PubMed 18483728Oder B, Loewe M, Reisegger M, Lang W, Ilias W, Thurnher SA. CT-guided ozone/steroid therapy for the treatment of degenerative spinal disease--effect of age, gender, disc pathology and multi-segmental changes. Neuroradiology. 2008 Sep;50(9):777-85. doi: 10.1007/s00234-008-0398-2. Epub 2008 May 16.
- BackgroundMixter WJ, Barr JS. Rupture of the intervertebral disc with involvement of the spinal canal. N Engl J Med 211:210-215, 1934.
- Background: PubMed 12748111Andreula CF, Simonetti L, De Santis F, Agati R, Ricci R, Leonardi M. Minimally invasive oxygen-ozone therapy for lumbar disk herniation. AJNR Am J Neuroradiol. 2003 May;24(5):996-1000.
- Background: PubMed 15081127Andreula C, Muto M, Leonardi M. Interventional spinal procedures. Eur J Radiol. 2004 May;50(2):112-9. doi: 10.1016/j.ejrad.2003.10.013.
- Background: PubMed 15891150Bonetti M, Fontana A, Cotticelli B, Volta GD, Guindani M, Leonardi M. Intraforaminal O(2)-O(3) versus periradicular steroidal infiltrations in lower back pain: randomized controlled study. AJNR Am J Neuroradiol. 2005 May;26(5):996-1000.
- Background: PubMed 17209164Gallucci M, Limbucci N, Zugaro L, Barile A, Stavroulis E, Ricci A, Galzio R, Masciocchi C. Sciatica: treatment with intradiscal and intraforaminal injections of steroid and oxygen-ozone versus steroid only. Radiology. 2007 Mar;242(3):907-13. doi: 10.1148/radiol.2423051934. Epub 2007 Jan 5.
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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.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AO-1000 in people with Disk, Herniated, run by ActiveO Inc. at 3 sites in Canada.
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 9 inclusion and 20 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 15 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Canada. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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.
What does the primary outcome measure?
Primary Effectiveness Endpoint: Change from Baseline ODI Score at 1 Month (time frame: 1 month post-treatment). The study lists 2 primary outcomes in all. 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 NCT01339377, which also lists 8 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 15 Jul 2016.