Anti-mycobacterium treatment reverses cerebral radiation necrosis

ISRCTN ISRCTN04023349
DOI https://doi.org/10.1186/ISRCTN04023349
Secondary identifying numbers N/A
Submission date
20/03/2013
Registration date
18/04/2013
Last edited
22/01/2019
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Background and study aims
Radiotherapy is used to treat a wide variety of head and neck tumors that arise in and around the skull base. Radiation-induced injury may occur when exposure of adjacent normal nervous system tissue to radiation is unavoidable. Acute injury is usually mild and transient, but the delayed radiation injury (DRI) of normal brain can be a devastating complication and generally occurs months to years after the initiation of therapy. DRI is generally progressive and irreversible, and have a tremendous negative impact on a patient’s quality of life. The mechanism of DRI is not well understood . DRI can occur even when the most stringent measures are taken to avoid exposing healthy tissue to harmful levels of radiation. To date, the treatment of DRI has typically been management of symptoms.
Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors that affects the southern Chinese population. Temporal lobe necrosis (TLN) is one of the most dreaded DRI complications in NPC after external radiation. Evaluation of the temporal lobes in patients previously treated for NPC can provide a better understanding of DRI in the brain unaffected by the underlying tumor outside of the planned field of radiation.
In 2008, we used anti-mycobacterium therapy (AMT) to treat a symptomatic TLN patient suffering headache and dysphasia, accompanied with pulmonary tuberculosis as evidenced by positive chest X-ray test. The AMT provided an unexpected symptom relief to TLN. Based on this experience, we have developed a trial protocol to evaluate whether AMT can reverse the disease in both symptoms and MRI abnormality.

Who can participate?
The study involves NPC patients who had undergone radiation therapy, suffering bilateral
temporal lobe necrosis. The age ranges from 18 to 65 years old.

What does the study involve?
Participants belong to one of two groups: active treatment group or control group.
In the AMT active treatment group, all former treatments with corticosteroids were discontinued for patients prior to AMT initiation.
In the control group, treatments were conducted with routine practices.

What are the possible benefits and risks of participating?
The main risks of treatment group are injuries to liver function and stomach. The treatment is carried out under extensive observation.

Where is the study run from?
The study is conducted at the First Affiliated Hospital of Sun Yat-sen University, Guangzhou (China)

When is the study starting and how long is it expected to run for?
January 2009 to June 2014.

Who is funding the study?
Grants from the Guangdong Natural Science Foundation (China).

Who is the main contact?
Prof.Yanqing Feng
fyqgz@vip.sina.com

Contact information

Prof Weixi Zhang
Scientific

58, Zhongshan 2 Road
Guangzhou
510080
China

Email weixizhang@qq.com

Study information

Study designProspective non-randomized controlled single-center study
Primary study designInterventional
Secondary study designNon randomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleEffects of anti-mycobacterium treatment on temporal lobe necrosis following radiotherapy for nasopharyngeal carcinoma: a prospective, controlled study
Study objectivesThe mechanisms of radiation-induced delayed brain injuries (DRI) remains poorly understood, and treatment with corticosteroids, surgery, and antioxidants is often ineffective. The aim of this study is to investigate whether temporal lobe necrosis, a severe type of DRI, can be reversed by anti-mycobacterium therapy (AMT).
Ethics approval(s)The SUN Yat-sen university ethics committee approved the study. The approval number is 2012(06). The date of approval is 18-Dec-2012. All patients were informed of the potential short- and long-term drug complications of AMT. Written informed consent was obtained from patients who agreed to participate in the study.
Health condition(s) or problem(s) studiedDelayed brain radiation injury/temporal lobe necrosis/oncology
InterventionIn the AMT active treatment group, all former treatments with corticosteroids were discontinued for patients prior to AMT initiation. Our initial treatment protocols (Treatment First Phase) comprised amikacin (600 mg/day) and mannitol 125 ml (bid) for 2 weeks, together with a three-drug AMT regimen (per day: isoniazid 8 mg/kg, rifampicin 10 mg/kg, pyrazinamide 25 mg/kg). Followed by treatment with a three-drug AMT regimen for nine months (Treatment Second Phase). And then by treatment with a combination of isoniazid and rifampicin with the same dosages that ceased after 24 months (Treatment Third Phase).
In the control group, treatments were conducted with routine practices including steroids, IVIG, Hyperbaric oxygen (HBO), nerve growth factor, and mannitol alone or combination during the observational period.
Intervention typeOther
Primary outcome measureThe Activities of daily living (ADL) were adopted to assess subjects’ neurological status. ADL were assessed by the Barthel Index (BI) (0–100 scale, with lower scores denoting less independence in activities of daily living)
Secondary outcome measuresEvaluation by MRI tests
Overall study start date01/01/2009
Completion date30/12/2014

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants60
Key inclusion criteriaPatients who fulfilled the following eligibility criteria were recruited in this study:
1. Aged 18 to 65 years
2. Histopathologically proven cases of NPC who had undergone radiation therapy, with
negative brain MR before RT
3. Patients must have received cranial irradiation ≥ 6 months prior to study entry
4. MRI evidence of bilateral temporal lobe edema and/or necrosis with
or without foci of contrast enhancement on MRI
5. Evidence of progressive neurologic signs or symptoms related with TLN
Key exclusion criteriaPatients were excluded if they had:
1. Significant hepatic or renal insufficiency
2. Evidence of brain metastasis, brain abscess, any intracranial tumor, cerebral infarction,
demyelinating disease
3. Clinical manifestations such as fever, meningeal irritatation signs indicating meningitis
Date of first enrolment01/01/2009
Date of final enrolment30/12/2014

Locations

Countries of recruitment

  • China

Study participating centre

58, Zhongshan 2 Road
Guangzhou
510080
China

Sponsor information

Sun Yat-sen University (China)
University/education

No. 135, Xingang Xi Road
Guangzhou
510275
China

Phone 86(20)87755766-8281
Email fyqgz@sina.com
Website http://www.sysu.edu.cn
ROR logo "ROR" https://ror.org/0064kty71

Funders

Funder type

Research organisation

Guangdong Natural Science Foundation (Grant nos.2012B03180067), China

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/09/2014 22/01/2019 Yes No

Editorial Notes

22/01/2019: Publication reference added