Systemic SclerosisNCT04826419
Effect of Ozone Therapy for the Treatment of Digital Ulcer in Patients With SSc
A study testing ozone therapy in people with Systemic Sclerosis, run by Pamukkale University at 1 site in Turkey (Türkiye).
Trial summary
Functionality in patients with SSc? Systemic Sclerosis (SSc) is a chronic connective tissue disease characterized by microvascular involvement, immunological dysfunction, extracellular matrix deposition in the skin and internal organ involvement. Vascular disease has an important role in the pathogenesis of SSc. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Systemic Sclerosis
- What is being tested?
- ozone therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 1 Apr 2021to 1 Jan 2022
- Phase
- Interventional
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- SSc patients who have no comorbidity
Who cannot join
- gangrenous ulcers
- calcinosis-free ulcers
- traumatic ulcers
- vasculitis
- active osteomyelitis
- hyperthyroidism
- pregnancy
- allergies to ozone therapy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Non-invazive Ozone Therapy and Digital Ulcer in Patients With SSc
Functionality in patients with SSc? Systemic Sclerosis (SSc) is a chronic connective tissue disease characterized by microvascular involvement, immunological dysfunction, extracellular matrix deposition in the skin and internal organ involvement. Vascular disease has an important role in the pathogenesis of SSc. Especially as a result of involvement of micro-vessel and digital arteries, digital ulcer (DU) formation may be seen. DUs are responsible for pain, poor quality of life, impairment of life activities and morbidity in patients with SSc. , they are correlated to disease severity and outcome. Approximately half of SSc patients have DU during the course of the disease. Recurrent DU is observed in 10% of the patients. In 75% of these patients, DU occurs 5 years after diagnosis. Patients with anti-SCL 70+ develop DU 5 years earlier than those with anti-centromere positive. The development of DU may take a long time to heal if there is underlying calcinosis. In a study, it was seen that the recovery of DU was 93.6 days if there is underlying calcinosis, and 76.2 days if not. DUs can be infected and thus complicated by osteomyelitis. In a retrospective study, it was reported that 42% of infected DUs were associated with osteomyelitis. DU management is a great challenge for the clinician and requires a multidisciplinary approach. Ozone has a place in medical use since the 19th century, as it is an oxidant and disinfectant. In recent studies, it has been reported to be antiviral and bactericidal. Therefore, it has indications such as coronary artery disease, chronic hepatitis and chronic low back pain. It has also been shown to have a positive role in trophic ulcer, ischemic ulcer and diabetic ulcer healing. The mechanism by which ozone therapy provides wound healing is not fully understood. In addition, it improves microcirculation in the capillary vessels by improving flexibility and stability of the cell membrane and limiting the aggregation and adhesion of platelets.
In the literature, it was stated in a study that ozone therapy was effective for the treatment of DU in SSc patients. In our study, we aimed to investigate the effect of ozone therapy on patients who are resistant to medical treatment and who have impaired quality of life for a long time.
Read the detailed description
Material-Method 34 SSc patients who were followed up in Pamukkale University Rheumatology due to DU are going to be included in the study. SSc is diagnosed and based on the American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) Criteria for the classification of SSc. Skin thickness will be evaluated with the Modified Rodnan Score.
DUs will be graded according to a scale developed by Amanzi et al. In 2010. Written informed consents were obtained from all patients before entry into the study, according to the Declaration of Helsinki and guidelines of the local ethics committee. The study was approved by Pamukkale University ethics committee. Among the patients included in the study, those with gangrenous ulcers, calcinosis-free ulcers, traumatic ulcers, vasculitis, active osteomyelitis, hyperthyroidism, pregnancy, and allergies to ozone therapy will be excluded from the study.
Baseline evaluation The demographic profile of SSc patients, therapy, scleroderma type, the onset of reynoud phenomenon (RF) RF disease duration, RFI time with the number of daily attacks, active and inactive digital ulcers count, ulcer size, pain, number of pitting, laboratory findings, and functional scales will recorded. Antinuclear antibodies (ANA), anti-centromere antibodies (ACA) and anti-topoisomerase antibodies (Scl70) will be studied from laboratory findings. An indirect immunofluorescent assay, for semi quantitative determination of anti-nuclear IgG antibodies (ANA) in patients' serum NOVA LITE™ IFA HEp-2 ANA Complete Kit was used. Antibodies to extractable nuclear antigens ACA and Scl70 are going to be determined by a commercial clinical enzyme linked immunosorbent assay (ELISA).
Functional parameters such as health assessment questionnaire (HAQ), visual analogue scale (VAS) and Modified Hand Mobility in Scleroderma Test (HAMISm) will be evaluated before treatment and on the 30th day.
Interventıon Group The treatment or clinical status of the SSc patients followed up with DU was reached by a blinded health professional by phone. Those who wanted to participate actively in the study formed the ozone group, but those who did not want to participate due to the pandemic constituted the control group.
Ozone Group The treatment session of oxygen-ozone was 80 mg/mL ozone (total volume: 60-100 mL) in a special bag using the ozone generator device (Humazon Promedic, German).
Treatment group Similar demographic results and treatment protocols area with treatment group consisted of SSc patients.
Outcomes Primary outcomes Ulcer healing was our primary outcome, which was assessed depending on Zhang andcolleagues ulcers grading where they graded ulcers into four levels, Grade 0 (no change), Grade 1 (wound size decreased less than ½); Grade 2 (wound size decreased more than ½) and Grade 3 (wound healing) (31). Ozone treatment were considered efficient if patients reached grade 1 to 3.
Secondary outcomes For our secondary outcomes both group were subjected to the following after two weeks and four weeks of intervention: they were reassessed for number of Raynaud's attacks/day, duration of Raynaud's attack, ulcer size in mm, ulcer pain was assessed by VAS and functional status evaluated by HAQ and HAMISm.
- Conditions
- Systemic Sclerosis
- Being tested
- ozone therapy
- Medical subject headings
- Scleroderma, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ozone therapyOther
The treatment session of oxygen-ozone was 80 mg/mL ozone (total volume: 60-100 mL) in a special bag using the ozone generator device (Humazon Promedic, German) five times a week for the first week.The treatment session of oxygen-ozone was 40 mg/mL ozone (total volume: 60-100 mL) in a special bag using the ozone generator device (Humazon Promedic, German) twice a week after first week.
| Study group | Role | What they receive |
|---|---|---|
| Non-invazive ozone therapy in a group | Active comparator | ozone therapy Receives: Other: ozone therapy |
| Control group | No intervention | control groups do not take ozone therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ulcer healing
Ulcer healing was our primary outcome, which was assessed depending on Zhang andcolleagues ulcers grading where they graded ulcers into four levels, Grade 0 (no change), Grade 1 (wound size decreased less than ½); Grade 2 (wound size decreased more than ½
Measured: one month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2021
- Study start1 Apr 2021
- Primary completion31 Dec 2021
- Study completion1 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Systemic SclerosisStudies of the same condition, open and under way.
- More trials run by Pamukkale 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
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomised-controlled trial
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pamukkale University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hakan Alkan, Pamukkale University
- Investigators
- Serdar Kaymaz, M.D, Principal investigator, Pamukkale U
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04826419
- Sponsor's protocol ID
- Pamukkale U
- Status last verified
- Jan 2022
- First submitted
- 29 Mar 2021
- Last updated
- 25 Jan 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: there is no plan
Publications
Zhang J, Guan M, Xie C, Luo X, Zhang Q, Xue Y. Increased growth factors play a role in wound healing promoted by noninvasive oxygen-ozone therapy in diabetic patients with foot ulcers. Oxid Med Cell Longev. 2014;2014:273475. doi: 10.1155/2014/273475. Epub 2014 Jun 24.
PubMed 25089169
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-invazive Ozone Therapy and Digital Ulcer in Patients With SSc
- ClinicalTrials.gov ID
- NCT04826419
- Acronym / sponsor ID
- Pamukkale U
- Conditions
- Systemic Sclerosis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Pamukkale UniversityUniversity, hospital or other
- Study start
- 1 Apr 2021 (actual)
- Primary completion
- 31 Dec 2021 (actual)
- Study completion
- 1 Jan 2022 (actual)
- First posted
- 1 Apr 2021 (actual)
- 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.
Functionality in patients with SSc? Systemic Sclerosis (SSc) is a chronic connective tissue disease characterized by microvascular involvement, immunological dysfunction, extracellular matrix deposition in the skin and internal organ involvement. Vascular disease has an important role in the pathogenesis of SSc. Especially as a result of involvement of micro-vessel and digital arteries, digital ulcer (DU) formation may be seen. DUs are responsible for pain, poor quality of life, impairment of life activities and morbidity in patients with SSc. , they are correlated to disease severity and outcome. Approximately half of SSc patients have DU during the course of the disease. Recurrent DU is observed in 10% of the patients. In 75% of these patients, DU occurs 5 years after diagnosis. Patients with anti-SCL 70+ develop DU 5 years earlier than those with anti-centromere positive. The development of DU may take a long time to heal if there is underlying calcinosis. In a study, it was seen that the recovery of DU was 93.6 days if there is underlying calcinosis, and 76.2 days if not. DUs can be infected and thus complicated by osteomyelitis. In a retrospective study, it was reported that 42% of infected DUs were associated with osteomyelitis. DU management is a great challenge for the clinician and requires a multidisciplinary approach. Ozone has a place in medical use since the 19th century, as it is an oxidant and disinfectant. In recent studies, it has been reported to be antiviral and bactericidal. Therefore, it has indications such as coronary artery disease, chronic hepatitis and chronic low back pain. It has also been shown to have a positive role in trophic ulcer, ischemic ulcer and diabetic ulcer healing. The mechanism by which ozone therapy provides wound healing is not fully understood. In addition, it improves microcirculation in the capillary vessels by improving flexibility and stability of the cell membrane and limiting the aggregation and adhesion of platelets.
In the literature, it was stated in a study that ozone therapy was effective for the treatment of DU in SSc patients. In our study, we aimed to investigate the effect of ozone therapy on patients who are resistant to medical treatment and who have impaired quality of life for a long time.
Detailed description
Material-Method 34 SSc patients who were followed up in Pamukkale University Rheumatology due to DU are going to be included in the study. SSc is diagnosed and based on the American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) Criteria for the classification of SSc. Skin thickness will be evaluated with the Modified Rodnan Score.
DUs will be graded according to a scale developed by Amanzi et al. In 2010. Written informed consents were obtained from all patients before entry into the study, according to the Declaration of Helsinki and guidelines of the local ethics committee. The study was approved by Pamukkale University ethics committee. Among the patients included in the study, those with gangrenous ulcers, calcinosis-free ulcers, traumatic ulcers, vasculitis, active osteomyelitis, hyperthyroidism, pregnancy, and allergies to ozone therapy will be excluded from the study.
Baseline evaluation The demographic profile of SSc patients, therapy, scleroderma type, the onset of reynoud phenomenon (RF) RF disease duration, RFI time with the number of daily attacks, active and inactive digital ulcers count, ulcer size, pain, number of pitting, laboratory findings, and functional scales will recorded. Antinuclear antibodies (ANA), anti-centromere antibodies (ACA) and anti-topoisomerase antibodies (Scl70) will be studied from laboratory findings. An indirect immunofluorescent assay, for semi quantitative determination of anti-nuclear IgG antibodies (ANA) in patients' serum NOVA LITE™ IFA HEp-2 ANA Complete Kit was used. Antibodies to extractable nuclear antigens ACA and Scl70 are going to be determined by a commercial clinical enzyme linked immunosorbent assay (ELISA).
Functional parameters such as health assessment questionnaire (HAQ), visual analogue scale (VAS) and Modified Hand Mobility in Scleroderma Test (HAMISm) will be evaluated before treatment and on the 30th day.
Interventıon Group The treatment or clinical status of the SSc patients followed up with DU was reached by a blinded health professional by phone. Those who wanted to participate actively in the study formed the ozone group, but those who did not want to participate due to the pandemic constituted the control group.
Ozone Group The treatment session of oxygen-ozone was 80 mg/mL ozone (total volume: 60-100 mL) in a special bag using the ozone generator device (Humazon Promedic, German).
Treatment group Similar demographic results and treatment protocols area with treatment group consisted of SSc patients.
Outcomes Primary outcomes Ulcer healing was our primary outcome, which was assessed depending on Zhang andcolleagues ulcers grading where they graded ulcers into four levels, Grade 0 (no change), Grade 1 (wound size decreased less than ½); Grade 2 (wound size decreased more than ½) and Grade 3 (wound healing) (31). Ozone treatment were considered efficient if patients reached grade 1 to 3.
Secondary outcomes For our secondary outcomes both group were subjected to the following after two weeks and four weeks of intervention: they were reassessed for number of Raynaud's attacks/day, duration of Raynaud's attack, ulcer size in mm, ulcer pain was assessed by VAS and functional status evaluated by HAQ and HAMISm.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- randomised-controlled trial
| Arm | Type | Receives |
|---|---|---|
| Non-invazive ozone therapy in a group | Active comparator | Other: ozone therapyozone therapy |
| Control group | No intervention | –control groups do not take ozone therapy |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- SSc patients who have no comorbidity
Key exclusion criteria (8 listed)
- gangrenous ulcers
- calcinosis-free ulcers
- traumatic ulcers
- vasculitis
- active osteomyelitis
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 |
|---|---|---|
| ozone therapyThe treatment session of oxygen-ozone was 80 mg/mL ozone (total volume: 60-100 mL) in a special bag using the ozone generator device (Humazon Promedic, German) five times a week for the first week.The treatment session of oxygen-ozone was 40 mg/mL ozone (total volume: 60-100 mL) in a special bag using the ozone generator device (Humazon Promedic, German) twice a week after first week. | Other | Non-invazive ozone therapy in a group |
Primary outcome
Ulcer healing
Time frame: one month
Ulcer healing was our primary outcome, which was assessed depending on Zhang andcolleagues ulcers grading where they graded ulcers into four levels, Grade 0 (no change), Grade 1 (wound size decreased less than ½); Grade 2 (wound size decreased more than ½
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 25 Jan 2022.
- Background: PubMed 25089169Zhang J, Guan M, Xie C, Luo X, Zhang Q, Xue Y. Increased growth factors play a role in wound healing promoted by noninvasive oxygen-ozone therapy in diabetic patients with foot ulcers. Oxid Med Cell Longev. 2014;2014:273475. doi: 10.1155/2014/273475. Epub 2014 Jun 24.
- Individual participant dataSharing planned: No. there is no plan
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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.
Serdar Kaymaz, M.D principal investigator
Pamukkale U
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing ozone therapy in people with Systemic Sclerosis, run by Pamukkale University at 1 site in Turkey (Türkiye).
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 1 inclusion and 8 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 25 Jan 2022. 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 Turkey (Türkiye). 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?
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?
Ulcer healing (time frame: one month). 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 NCT04826419, 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 25 Jan 2022.