The effect of the addition of carbogen inhalation and nicotinamide to conventional chemotherapy for hypoxia parameters in non-Hodgkin lymphoma patients
| ISRCTN | ISRCTN77237304 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN77237304 |
| Secondary identifying numbers | EAP-HYP-1 |
- Submission date
- 06/06/2021
- Registration date
- 14/06/2021
- Last edited
- 12/07/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Plain English Summary
Background and study aims
Diffuse large B-cell lymphoma (DLBCL) is one of the most common blood cancers in the world. Chemotherapy with R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone) has been standard treatment for almost 40 years with a remission rate of about 60-70%. Tumor hypoxia (the situation where tumor cells have been deprived of oxygen) plays an important role in cancer growth, survival, and spread. The aim of this study is to test the effect of modulating tumor hypoxia with nicotinamide/vitamin B3 and carbogen inhalation (95% oxygen and 5% carbon dioxide) in DLBCL patients who experience tissue hypoxia.
Who can participate?
Patients aged 18-65 with DLBCL and proven tumor hypoxia
What does the study involve?
Participants are randomly allocated to be treated with nicotinamide/vitamin B3 and carbogen inhalation or no additional treatment. Tumor size reduction and blood parameters are measured before and after 1 cycle of chemotherapy.
What are the possible benefits and risks of participating?
Patients in the study group might have a better reduction in tumor size after chemotherapy but might have adverse events such as hot flushing, headache, and itching.
Where is the study run from?
Kariadi General Hospital (Indonesia)
When is the study starting and how long is it expected to run for?
January 2021 to May 2022
Who is funding the study?
Investigator initiated and funded
Who is the main contact?
Eko Adhi Pangarsa
ekoadhi90@gmail.com
Contact information
Scientific
Sutomo St. No. 18
Semarang
50244
Indonesia
 ORCID ID |
0000-0001-5003-1292 |
|---|---|
| Phone | +62 (0)8122844758 |
| ekopangarsa90@gmail.com |
Scientific
Sutomo St. No. 18
Semarang
50244
Indonesia
| ORCID ID |
0000-0003-0176-7310 |
|---|---|
| Phone | +62 (0)82248748476 |
| danielrizky@hotmail.co.id |
Study information
| Study design | Single-center open-label randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | The effect of the addition of carbogen inhalation and nicotinamide to conventional chemotherapy against hypoxia, angiogenesis, apoptotic pathway, glycolytic metabolism, and inflammatory pathway parameters in diffuse large B-cell lymphoma patients |
| Study hypothesis | There is an effect of giving inhaled carbogen-nicotinamide addition on the hypoxia, angiogenesis, apoptotic pathway, glycolytic metabolism, and inflammatory pathway parameters in diffuse large B-cell lymphoma (DLBCL) patients who experience tissue hypoxia and receive R-CHOP (rituximab, cyclophosphamide, vincristin, doxorubicin, prednisone) chemotherapy. |
| Ethics approval(s) | Approved 08/02/2021, Health Research Ethics Committee RSUP Dr. Kariadi Semarang (Sutomo St. no. 18, Semarang, Indonesia; +62 (0)24 8413476; kepk.rskariadi@gmail.com), ref: 736/EC/KEPK-RSDK/2021 |
| Condition | Diffuse large B-cell lymphoma |
| Intervention | Participants are randomised by simple random sampling. Patients in the study arm will take nicotinamide 2 g 1 hour before chemotherapy and inhale 10 liters/min carbogen for 10 minutes on and off, starting 10 minutes before R-CHOP chemotherapy until the finish. The control group will not receive any intervention. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Nicotinamide, carbogen (oxygen 95% & CO₂ 5%) |
| Primary outcome measure | Tumor size measured with blood oxygenation level dependent (BOLD) MRI before chemotherapy and 1 week after 1st cycle of R-CHOP chemotherapy |
| Secondary outcome measures | 1. Hypoxia parameters (HIF-1 alpha & miRNA-210 serum) measured using ELISA and qRT PCR, respectively 2. Angiogenesis parameters (VEGF serum) measured using ELISA 3. Glycolytic parameters (lactate and blood gas analysis) measured using enzymatic and colorimetric methods and ion-selective electrode, respectively 4. Apoptotic parameters (p53, BCL-2 serum) measured using ELISA 5. Inflammatory parameters (TNF-alpha, sIL-2R serum) measured using ELISA 6. Safety and adverse events of the intervention categorized by Common Terminology Criteria for Adverse Events (CTCAE) v6.0 and monitored during carbogen intervention and 1 day after Timepoints: Study group: measured before chemotherapy, 10 minutes after carbogen and nicotinamide, and 1 week after 1st cycle of R-CHOP Control group: measured before chemotherapy and 1 week after 1st cycle of R-CHOP |
| Overall study start date | 01/01/2021 |
| Overall study end date | 31/05/2022 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 65 Years |
| Sex | Both |
| Target number of participants | 40 |
| Total final enrolment | 40 |
| Participant inclusion criteria | 1. DLBCL patients with increased expression of HIF-1α (>10%) via tissue immunohistochemistry 2. Do not have anemia (hemoglobin ≥11 g/dl) 3. Age 18-65 years 4. Do not have obstructive pulmonary disease (normal x-ray thorax and spirometry) 5. No heart problems (normal electrocardiogram (ECG) and/or normal left ventricular ejection fraction (LVEF) echocardiography) 6. Have no cerebrovascular disease 7. Do not experience severe liver function problems 8. No severe renal function impairment 9. Do not suffer from diabetes mellitus (fasting blood glucose ˂126 mg/dl or random blood glucose <200 mg/dl) |
| Participant exclusion criteria | 1. Eastern Cooperative Oncology Group (ECOG) ≥2 2. Pregnancy before or while undergoing chemotherapy 3. History of chemotherapy for non-Hodgkin lymphoma (NHL) cases before 4. Allergic reaction to chemotherapy treatment |
| Recruitment start date | 02/07/2021 |
| Recruitment end date | 30/05/2022 |
Locations
Countries of recruitment
- Indonesia
Study participating centre
Semarang
50244
Indonesia
Sponsor information
Hospital/treatment centre
Sutomo no. 18
Semarang
50244
Indonesia
| Phone | +62 (0)24 8413476 |
|---|---|
| info@rskariadi.co.id | |
| Website | http://www.rskariadi.co.id/ |
"ROR" |
https://ror.org/040f86t49 |
Funders
Funder type
Other
No information available
Results and Publications
| Intention to publish date | 01/09/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from Daniel Rizky (danielrizky@hotmail.co.id). Raw datasets will be available for 5 years. Informed consent will be obtained directly from the patients, and the patient’s identity will be hidden using initials. There are no ethical or legal restrictions. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Basic results | 12/07/2023 | No | No |
Additional files
Editorial Notes
12/07/2023: The basic results have been uploaded to the study outputs table.
01/08/2022: The following changes were made to the trial record:
1. The recruitment start date was changed from 01/06/2021 to 02/07/2021.
2. The recruitment end date was changed from 01/01/2022 to 30/05/2022.
3. The overall trial end date was changed from 01/02/2022 to 31/05/2022.
4. The intention to publish date was changed from 02/02/2022 to 01/09/2022.
5. Total final enrolment added.
08/06/2021: Trial's existence confirmed by the Health Research Ethics Committee RSUP Dr. Kariadi Semarang.
