Cryotherapy EffectNCT03203733
Cryoprotection of Chemotherapy-induced Oral Mucositis After Autologous Stem Cell Transplantation, a Randomized Study
A study testing Cooral™ and cryotherapy in people with Cryotherapy Effect, run by Uppsala University at 5 sites in 2 countries.
Trial summary
This study evaluates, among study patients with lymphoma or myeloma undergoing autologous SCT, whether cooling oral mucosa with a cooling device compared with ice cubes/crushed ice or ice pop succeeds in reducing the degree of oral mucositis (OM) according to the Oral Mucositis Assessment Scale (OMAS) total,degree of… Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Cryotherapy Effect
- What is being tested?
- Cooral™ and cryotherapy
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 182 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 12 Jun 2017to 31 Dec 2019
- 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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients between 16 and 99 years of age diagnosed with lymphoma or myeloma
- Able to communicate in Swedish
- Treated with bis-chloroethylnitrosourea, etoposide, cytarabine, and cyclophosphamide(BEAC) or bis-chloroethylnitrosourea, etoposide, cytarabine, and melphalan (BEAM) (lymphoma diagnosis), melphalan (myeloma diagnosis), before stem cell transplantation (SCT)
Who cannot join
- Patients who do not understand oral and written information in Swedish.
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
Sweden4 sites
Linköping University Hospital
Linköping
Örebro University Hospital
Örebro
Karolinska University Hospital
Stockholm
Uppsala University Hospital
Uppsala
About this study
This study evaluates, among study patients with lymphoma or myeloma undergoing autologous SCT, whether cooling oral mucosa with a cooling device compared with ice cubes/crushed ice or ice pop succeeds in reducing the degree of oral mucositis (OM) according to the Oral Mucositis Assessment Scale (OMAS) total,degree of OM according to World Health Organisation (WHO), tolerability of either cooling method. The study is also aiming to , patients subjective experience of OM, rating of general quality of life and oral pain, number of days with total parenteral nutrition (TPN), number of hospital days, total dose of opioids, and C reactive protein during time in care.
Finally, the study aims to evaluate weight loss, Leukocyte particle concentration, number of days until bone marrow response, S-albumin, and body temperature.
Read the detailed description
The degree of OM is assessed at eight intraoral locations, in accordance with the Oral Mucositis Assessment Scale (OMAS) (graded 0-3 for ulceration and 0-2 for erythema). 0 corresponds to "normal" while 3 and 2 are "sore >3 cm2" and "severe erythema" respectively. The assessment generates both an average for OMAS ulceration (0-3) and OMAS erythema (0-2) and a total average OMAS (0-5), which is the mean of both ulceration and erythema.
Besides OMAS, ulceration and erythema are also assessed with the WHO scale (graded 0-4) where 0 is "no mucositis" and 4 is "ulceration, total parenteral nutrition".
Assessment with OMAS and WHO is done by a dentist, blinded to treatment group, three times a week, for example, Monday, Wednesday, Friday, until discharge or at most day +28.Assessment with the WHO is also performed by nurses who are not blinded to the treatment group, three times a week.
Furthermore, the patients, after cooling ends, assess the tolerability of the respective cooling method with the aid of a questionnaire developed for the study. The questionnaire is intended to give some idea of any discomfort or side effects the patients feel as a result of the cooling method.
The patients assess their perception of oral problems daily with the aid of specific questions in a diary developed for the study. The questions are intended to give a picture of the effect of OM on the patient's general status.
General quality of life is assessed twice during the study period, before the start of treatment and at discharge, with a validated quality of life instrument.
Oral pain is assessed with a visual analog scale (VAS) with the extremes graded on a 10-figure scale (0-10) where 0 is "no pain" and 10 is "unbearable pain".
Information about total parenteral nutrition (TPN), number of hospital days, total dose of opioids, weight loss, and body temperature will be retrieved from patient records. Laboratory results of blood tests will be retrieved from each department's register of test results.
The result of the assessments is documented on sheets for the purpose in a patient's individual kardex.
- Conditions
- Cryotherapy Effect
- Being tested
- Cooral™, cryotherapy
- Keywords
- Oral Mucositis , cooling, cryotherapy
- Medical subject headings
- Stomatitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cooral™Device
An intraoral cooling device which is as effective as ice but with better patient comfort. The cooling device has the advantage that the water temperature can be modified. It enables that the unacceptable low temperatures that occur with ice cooling can be avoided.
cryotherapyOther
Oral cooling by ice chips or crushed ice or ice pop
| Study group | Role | What they receive |
|---|---|---|
| 'Cooral™' | Experimental | oral cooling with use of cooling device Receives: Device: Cooral™ |
| cryotherapy | Active comparator | Cryoterapy consists of ice cubes or crossed ice and used as standard treatment for oral cooling. Receives: Other: cryotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
OM according to OMAS total during 28 days or until discharge
Assesment with OMAS is done by a dentist blinded to treatment group, three times a week during 28 days or until discharge. Assessment with the not blinded to the treatment group, three times a week during 28 days or until discharge.
Measured: 28 days or until discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2017
- Study start12 Jun 2017
- Primary completion6 Dec 2019
- Study completion31 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Cryotherapy EffectStudies of the same condition, open and under way.
- More trials run by Uppsala 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 182 participants (actual)
Sponsor and investigators
- Lead sponsor
- Uppsala University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Karin Garming Legert, Dentist, PhD, Principal investigator, Section for Orofacial diagnosis and surgery, Karolinska University HospitalMats Jontell, dentist, Study director, Oral Medicine Clinic, Department of Odontology, University of GothenburgTorbjörn Karlsson, MD physician, Principal investigator, Section for Hematology & Coagulation, Uppsala University HospitalPA Broliden, MD, PhD,, Principal investigator, Hematology Center, M54, Karolinska University HospitalFranz Rommel, physician, Principal investigator, Section for Hematology, Linköping University HospitalErik Ahlstrand, physician, Principal investigator, Section for Hematology, Örebro University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03203733
- Sponsor's protocol ID
- BraincoolUppsalaU
- Status last verified
- Nov 2020
- First submitted
- 9 Jun 2017
- Last updated
- 20 Nov 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Peterson DE, Bensadoun RJ, Roila F; ESMO Guidelines Working Group. Management of oral and gastrointestinal mucositis: ESMO Clinical Practice Guidelines. Ann Oncol. 2011 Sep;22 Suppl 6(Suppl 6):vi78-84. doi: 10.1093/annonc/mdr391. No abstract available.
PubMed 21908510Lalla RV, Bowen J, Barasch A, Elting L, Epstein J, Keefe DM, McGuire DB, Migliorati C, Nicolatou-Galitis O, Peterson DE, Raber-Durlacher JE, Sonis ST, Elad S; Mucositis Guidelines Leadership Group of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO). MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2014 May 15;120(10):1453-61. doi: 10.1002/cncr.28592. Epub 2014 Feb 25.
PubMed 24615748Elting LS, Keefe DM, Sonis ST, Garden AS, Spijkervet FK, Barasch A, Tishler RB, Canty TP, Kudrimoti MK, Vera-Llonch M; Burden of Illness Head and Neck Writing Committee. Patient-reported measurements of oral mucositis in head and neck cancer patients treated with radiotherapy with or without chemotherapy: demonstration of increased frequency, severity, resistance to palliation, and impact on quality of life. Cancer. 2008 Nov 15;113(10):2704-13. doi: 10.1002/cncr.23898.
PubMed 18973181Naidu MU, Ramana GV, Rani PU, Mohan IK, Suman A, Roy P. Chemotherapy-induced and/or radiation therapy-induced oral mucositis--complicating the treatment of cancer. Neoplasia. 2004 Sep-Oct;6(5):423-31. doi: 10.1593/neo.04169.
PubMed 15548350Legert KG, Remberger M, Ringden O, Heimdahl A, Dahllof G. Reduced intensity conditioning and oral care measures prevent oral mucositis and reduces days of hospitalization in allogeneic stem cell transplantation recipients. Support Care Cancer. 2014 Aug;22(8):2133-40. doi: 10.1007/s00520-014-2190-7. Epub 2014 Mar 20.
PubMed 24647488Rubenstein EB, Peterson DE, Schubert M, Keefe D, McGuire D, Epstein J, Elting LS, Fox PC, Cooksley C, Sonis ST; Mucositis Study Section of the Multinational Association for Supportive Care in Cancer; International Society for Oral Oncology. Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis. Cancer. 2004 May 1;100(9 Suppl):2026-46. doi: 10.1002/cncr.20163.
PubMed 15108223Ibrahim A, Mahmoud D, Mavandadipur H, Walladbegi J. Interrater reliability in the assessment of oral mucositis among patients receiving high-dose chemotherapy: a multicenter comparison between specialized dentists and registered nurses. BMC Cancer. 2025 Dec 17;25(1):1874. doi: 10.1186/s12885-025-14670-3.
PubMed 41408611Walladbegi J, Henriksson R, Tavelin B, Svanberg A, Larfors G, Jadersten M, Schjesvold F, Mahdi A, Garming Legert K, Peterson DE, Jontell M. Efficacy of a novel device for cryoprevention of oral mucositis: a randomized, blinded, multicenter, parallel group, phase 3 trial. Bone Marrow Transplant. 2022 Feb;57(2):191-197. doi: 10.1038/s41409-021-01512-6. Epub 2021 Nov 3.
PubMed 34728786Walladbegi J, Svanberg A, Gellerstedt M. Protocol for a randomised controlled trial to study cryoprevention of chemotherapy-induced oral mucositis after autologous stem cell transplantation. BMJ Open. 2018 Oct 24;8(10):e021993. doi: 10.1136/bmjopen-2018-021993.
PubMed 30361399
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cryoprotection of Chemotherapy-induced Oral Mucositis After Autologous Stem Cell Transplantation, a Randomized Study
- ClinicalTrials.gov ID
- NCT03203733
- Acronym / sponsor ID
- BraincoolUppsalaU
- Conditions
- Cryotherapy Effect
- Keywords
- Oral Mucositis , cooling, cryotherapy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 182 participants (actual)
- Lead sponsor
- Uppsala UniversityUniversity, hospital or other
- Study start
- 12 Jun 2017 (actual)
- Primary completion
- 6 Dec 2019 (actual)
- Study completion
- 31 Dec 2019 (actual)
- First posted
- 29 Jun 2017 (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.
This study evaluates, among study patients with lymphoma or myeloma undergoing autologous SCT, whether cooling oral mucosa with a cooling device compared with ice cubes/crushed ice or ice pop succeeds in reducing the degree of oral mucositis (OM) according to the Oral Mucositis Assessment Scale (OMAS) total,degree of OM according to World Health Organisation (WHO), tolerability of either cooling method. The study is also aiming to , patients subjective experience of OM, rating of general quality of life and oral pain, number of days with total parenteral nutrition (TPN), number of hospital days, total dose of opioids, and C reactive protein during time in care.
Finally, the study aims to evaluate weight loss, Leukocyte particle concentration, number of days until bone marrow response, S-albumin, and body temperature.
Detailed description
The degree of OM is assessed at eight intraoral locations, in accordance with the Oral Mucositis Assessment Scale (OMAS) (graded 0-3 for ulceration and 0-2 for erythema). 0 corresponds to "normal" while 3 and 2 are "sore >3 cm2" and "severe erythema" respectively. The assessment generates both an average for OMAS ulceration (0-3) and OMAS erythema (0-2) and a total average OMAS (0-5), which is the mean of both ulceration and erythema.
Besides OMAS, ulceration and erythema are also assessed with the WHO scale (graded 0-4) where 0 is "no mucositis" and 4 is "ulceration, total parenteral nutrition".
Assessment with OMAS and WHO is done by a dentist, blinded to treatment group, three times a week, for example, Monday, Wednesday, Friday, until discharge or at most day +28.Assessment with the WHO is also performed by nurses who are not blinded to the treatment group, three times a week.
Furthermore, the patients, after cooling ends, assess the tolerability of the respective cooling method with the aid of a questionnaire developed for the study. The questionnaire is intended to give some idea of any discomfort or side effects the patients feel as a result of the cooling method.
The patients assess their perception of oral problems daily with the aid of specific questions in a diary developed for the study. The questions are intended to give a picture of the effect of OM on the patient's general status.
General quality of life is assessed twice during the study period, before the start of treatment and at discharge, with a validated quality of life instrument.
Oral pain is assessed with a visual analog scale (VAS) with the extremes graded on a 10-figure scale (0-10) where 0 is "no pain" and 10 is "unbearable pain".
Information about total parenteral nutrition (TPN), number of hospital days, total dose of opioids, weight loss, and body temperature will be retrieved from patient records. Laboratory results of blood tests will be retrieved from each department's register of test results.
The result of the assessments is documented on sheets for the purpose in a patient's individual kardex.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 'Cooral™' | Experimental | Device: Cooral™oral cooling with use of cooling device |
| cryotherapy | Active comparator | Other: cryotherapyCryoterapy consists of ice cubes or crossed ice and used as standard treatment for oral cooling. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Patients between 16 and 99 years of age diagnosed with lymphoma or myeloma
- Able to communicate in Swedish
- Treated with bis-chloroethylnitrosourea, etoposide, cytarabine, and cyclophosphamide(BEAC) or bis-chloroethylnitrosourea, etoposide, cytarabine, and melphalan (BEAM) (lymphoma diagnosis), melphalan (myeloma diagnosis), before stem cell transplantation (SCT)
Key exclusion criteria (1 listed)
- Patients who do not understand oral and written information in Swedish.
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 |
|---|---|---|
| Cooral™An intraoral cooling device which is as effective as ice but with better patient comfort. The cooling device has the advantage that the water temperature can be modified. It enables that the unacceptable low temperatures that occur with ice cooling can be avoided. | Device | 'Cooral™' |
| cryotherapyOral cooling by ice chips or crushed ice or ice pop | Other | cryotherapy |
Primary outcome
OM according to OMAS total during 28 days or until discharge
Time frame: 28 days or until discharge
Assesment with OMAS is done by a dentist blinded to treatment group, three times a week during 28 days or until discharge. Assessment with the not blinded to the treatment group, three times a week during 28 days or until discharge.
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 20 Nov 2020.
- Background: PubMed 21908510Peterson DE, Bensadoun RJ, Roila F; ESMO Guidelines Working Group. Management of oral and gastrointestinal mucositis: ESMO Clinical Practice Guidelines. Ann Oncol. 2011 Sep;22 Suppl 6(Suppl 6):vi78-84. doi: 10.1093/annonc/mdr391. No abstract available.
- Background: PubMed 24615748Lalla RV, Bowen J, Barasch A, Elting L, Epstein J, Keefe DM, McGuire DB, Migliorati C, Nicolatou-Galitis O, Peterson DE, Raber-Durlacher JE, Sonis ST, Elad S; Mucositis Guidelines Leadership Group of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO). MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2014 May 15;120(10):1453-61. doi: 10.1002/cncr.28592. Epub 2014 Feb 25.
- Background: PubMed 18973181Elting LS, Keefe DM, Sonis ST, Garden AS, Spijkervet FK, Barasch A, Tishler RB, Canty TP, Kudrimoti MK, Vera-Llonch M; Burden of Illness Head and Neck Writing Committee. Patient-reported measurements of oral mucositis in head and neck cancer patients treated with radiotherapy with or without chemotherapy: demonstration of increased frequency, severity, resistance to palliation, and impact on quality of life. Cancer. 2008 Nov 15;113(10):2704-13. doi: 10.1002/cncr.23898.
- Background: PubMed 15548350Naidu MU, Ramana GV, Rani PU, Mohan IK, Suman A, Roy P. Chemotherapy-induced and/or radiation therapy-induced oral mucositis--complicating the treatment of cancer. Neoplasia. 2004 Sep-Oct;6(5):423-31. doi: 10.1593/neo.04169.
- Background: PubMed 24647488Legert KG, Remberger M, Ringden O, Heimdahl A, Dahllof G. Reduced intensity conditioning and oral care measures prevent oral mucositis and reduces days of hospitalization in allogeneic stem cell transplantation recipients. Support Care Cancer. 2014 Aug;22(8):2133-40. doi: 10.1007/s00520-014-2190-7. Epub 2014 Mar 20.
- Background: PubMed 15108223Rubenstein EB, Peterson DE, Schubert M, Keefe D, McGuire D, Epstein J, Elting LS, Fox PC, Cooksley C, Sonis ST; Mucositis Study Section of the Multinational Association for Supportive Care in Cancer; International Society for Oral Oncology. Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis. Cancer. 2004 May 1;100(9 Suppl):2026-46. doi: 10.1002/cncr.20163.
- Derived from this study: PubMed 41408611Ibrahim A, Mahmoud D, Mavandadipur H, Walladbegi J. Interrater reliability in the assessment of oral mucositis among patients receiving high-dose chemotherapy: a multicenter comparison between specialized dentists and registered nurses. BMC Cancer. 2025 Dec 17;25(1):1874. doi: 10.1186/s12885-025-14670-3.
- Derived from this study: PubMed 34728786Walladbegi J, Henriksson R, Tavelin B, Svanberg A, Larfors G, Jadersten M, Schjesvold F, Mahdi A, Garming Legert K, Peterson DE, Jontell M. Efficacy of a novel device for cryoprevention of oral mucositis: a randomized, blinded, multicenter, parallel group, phase 3 trial. Bone Marrow Transplant. 2022 Feb;57(2):191-197. doi: 10.1038/s41409-021-01512-6. Epub 2021 Nov 3.
- Derived from this study: PubMed 30361399Walladbegi J, Svanberg A, Gellerstedt M. Protocol for a randomised controlled trial to study cryoprevention of chemotherapy-induced oral mucositis after autologous stem cell transplantation. BMJ Open. 2018 Oct 24;8(10):e021993. doi: 10.1136/bmjopen-2018-021993.
- Individual participant dataSharing planned: No
Related trials for Cryotherapy Effect
Recruiting
Effect of Cryotherapeutic and Nanotherapeutic Sodium Hypochlorite on Post-Operative Endodontic Pain.
Symptomatic Irreversible Pulpitis, Symptomatic Apical Periodontitis
Not yet recruitingPhase 3
Submucosal Cryotherapy and Anti-inflammatory Drugs for Postoperative Pain Following Root Canal Treatment in Maxillary Molars
Pulpitis
Recruiting
Intracoronary Cryotherapy Effect on Stabilization of Vulnerable Plaque in Patients With Stable Angina or ACS - A Traditional Feasibility Study
Coronary Arterial Disease (CAD), Plaque
Not yet recruiting
Effect of Intracanal Cryotherapy on Pain, Anxiety, and Salivary Irisin After Root Canal Treatment
Postoperative Pain After Endodontic Treatment, Dental Anxiety
Not yet recruiting
VibraCool Device to Reduce Pain and Opioid Use After Anterior Cruciate Ligament Reconstruction (ACLR)
ACL, Opioid Use
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.
Karin Garming Legert, Dentist, PhD principal investigator
Section for Orofacial diagnosis and surgery, Karolinska University Hospital
Mats Jontell, dentist study director
Oral Medicine Clinic, Department of Odontology, University of Gothenburg
Torbjörn Karlsson, MD physician principal investigator
Section for Hematology & Coagulation, Uppsala University Hospital
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cooral™ and cryotherapy in people with Cryotherapy Effect, run by Uppsala University at 5 sites in 2 countries.
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 3 inclusion and 1 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 20 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Sweden, Norway. 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?
OM according to OMAS total during 28 days or until discharge (time frame: 28 days or until discharge). 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 NCT03203733, which also lists 9 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 20 Nov 2020.