Condition category
Cancer
Date applied
20/03/2013
Date assigned
18/04/2013
Last edited
30/04/2013
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

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

Trial website

Contact information

Type

Scientific

Primary contact

Prof Weixi Zhang

ORCID ID

Contact details

58
Zhongshan 2 Road
Guangzhou
510080
China
weixizhang@qq.com

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Effects of anti-mycobacterium treatment on temporal lobe necrosis following radiotherapy for nasopharyngeal carcinoma: a prospective, controlled study

Acronym

Study hypothesis

The 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

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.

Study design

Prospective non-randomized controlled single-center study

Primary study design

Interventional

Secondary study design

Non randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Delayed brain radiation injury/temporal lobe necrosis/oncology

Intervention

In 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 type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

The 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 measures

Evaluation by MRI tests

Overall trial start date

01/01/2009

Overall trial end date

30/12/2014

Reason abandoned

Eligibility

Participant inclusion criteria

Patients 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

60

Participant exclusion criteria

Patients 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

Recruitment start date

01/01/2009

Recruitment end date

30/12/2014

Locations

Countries of recruitment

China

Trial participating centre

58, Zhongshan 2 Road
Guangzhou
510080
China

Sponsor information

Organisation

Sun Yat-sen University (China)

Sponsor details

No. 135
Xingang Xi Road
Guangzhou
510275
China
86(20)87755766-8281
fyqgz@sina.com

Sponsor type

University/education

Website

http://www.sysu.edu.cn

Funders

Funder type

Research organisation

Funder name

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

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes