Malignant GliomasALAgliomaNCT02155452
Fluorescence and Glioma Heterogeneity
An observational study of Malignant Gliomas, run by Tata Memorial Hospital at 1 site in India.
Trial summary
The investigators aim to study the heterogeneity of fluorescence within malignant gliomas by sampling tissues from these variable areas within the same tumor. These tissue samples will then be subjected to pathological and biological analysis to assess proteins related to ALA metabolism and correlated with the… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Malignant Gliomas
- What is being tested?
- ALA
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- How many people
- 25 participants
- Where
- 1 siteIndia
- Study dates
- May 2014to Jul 2019
- Phase
- Observational
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with malignant glioma
Who may be able to join
- Per-primum glioma
- Adults (18-65 years)
- Radiologically suspected malignant gliomas
- Variable contrast enhancement on MRI (patchy and/or non-uniform)
- Eligible for surgical therapy (craniotomy NOT stereotactic biopsy )
- No contraindication for surgery
Who cannot join
- Poor general condition (KPS < 70)
- Prior treatment (except biopsy)
- Compromised renal/hepatic function
- Immunocompromised status
- Known photosensitivity / allergy to 5-ALA
Trial locations and contacts
1 site in 1 country.
India1 site
Advanced Centre for Treatment, Research & Education in Cancer (ACTREC)
Navi Mumbai, Maharashtra, 410210
About this study
Official title: Understanding the Mechanisms of ALA-induced Fluorescence in Malignant Gliomas - Exploring the Biological Basis of Tumoral Heterogeneity.
The investigators aim to study the heterogeneity of fluorescence within malignant gliomas by sampling tissues from these variable areas within the same tumor. These tissue samples will then be subjected to pathological and biological analysis to assess proteins related to ALA metabolism and correlated with the fluorescence emitted as well as levels of protoporphyrin IX in the tissues.
Read the detailed description
Malignant gliomas are the commonest malignant brain tumors but are extremely challenging to treat. Neuro-oncology has seen little progress in its treatment despite extensive research. Extent of resection remains a very important prognostic factor in these tumors. Better the resection, better the outcomes. However resecting these tumors is not very easy primarily due to their infiltrative nature and difficulty in discerning tumor boundaries intraoperatively. Fluorescence guided resection (FGR) has recently been shown to be a very important and useful adjunct in maximizing this goal. FGR involves administration of aminolevulinic acid (ALA) to the patient prior to surgery. The ALA is converted to protoporphyrin IX (PPIX) in glioma cells. The PPIX is a fluorophore and can be visualized intraoperatively using a suitably modified microscope. Neurosurgeons can then resect the tumor radically guided by this fluorescence which is superior to the conventional microscopic resection. Selective PPIX accumulation in glioma cells is the key to the accuracy of this technique. The biological basis of selectivity of PPIX accumulation within glioma cells is however poorly understood. Various mechanisms could be involved starting from variable transport (related to blood-brain barrier properties), differential uptake (governed by active transport mechanisms) and differential metabolism within the cell. Understanding these mechanisms can lead to refinements in this strategy, overcoming its present limitations and development of methods to extend its scope.
- Conditions
- Malignant Gliomas
- Being tested
- ALA
- Keywords
- ALA, Malignant gliomas
- Medical subject headings
- Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALAProcedure or surgery
Also called 5- ALA
Prior to surgery all patients would receive freshly prepared solution of 5-ALA, 20 mg/kg bodyweight dissolved in 100 ml of potable water orally approximately 4 hours (range 4-6 hrs) before the commencement of anesthesia induction for surgery.
The surgery would then be performed with the help of navigation. After craniotomy, the navigation software would be used to identify the selected target areas based on the preoperative images (MR as well as PET when available) and directed image-guided biopsies from these representative areas will be collected for histological evaluation
| Study group | Role | What they receive |
|---|---|---|
| With ALA | Patients with malignant glioma. 25 patients will be provided the ALA for inducing fluorescence Receives: Procedure: ALA | |
| Without ALA | 5 tumor tissue samples from ACTREC tumor tissue repository will be obtained. These would be malignant gliomas or other brain tumor samples where ALA is usually not administered and will be used as controls and for calibration purposes |
What is being measured
The primary outcome is the main question the study is designed to answer.
Degree of fluorescence
- Degree of fluorescence in different tumor regions
- PPIX Qualification
Measured: At the time of surgery within 72 hours
Secondary outcomes (1)
High throughput proteomic screening of tissue samples
-A quantitative approach will be undertaken to compare the proteome profile
Measured: Postoperatively within 1 week of the excision
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2014 (estimated)
- Study startMay 2014
- Primary completionJul 2019
- Study completionJul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant GliomasStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Other
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tata Memorial Hospital
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Dr Aliasgar V Moiyadi, Tata Memorial Hospital
- Investigators
- Aliasgar V Moiyadi, MCh DNB, Principal investigator, neurosurgeon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02155452
- Sponsor's protocol ID
- TMC- ACTREC IRB project no 139
- Acronym
- ALAglioma
- Status last verified
- May 2022
- First submitted
- 17 May 2014
- Last updated
- 6 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Understanding the Mechanisms of ALA-induced Fluorescence in Malignant Gliomas - Exploring the Biological Basis of Tumoral Heterogeneity.
- ClinicalTrials.gov ID
- NCT02155452
- Acronym / sponsor ID
- ALAglioma / TMC- ACTREC IRB project no 139
- Conditions
- Malignant Gliomas
- Keywords
- ALA, Malignant gliomas
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Tata Memorial HospitalOther government
- Study start
- May 2014
- Primary completion
- Jul 2019 (actual)
- Study completion
- Jul 2019 (actual)
- First posted
- 4 Jun 2014 (estimated)
- 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.
The investigators aim to study the heterogeneity of fluorescence within malignant gliomas by sampling tissues from these variable areas within the same tumor. These tissue samples will then be subjected to pathological and biological analysis to assess proteins related to ALA metabolism and correlated with the fluorescence emitted as well as levels of protoporphyrin IX in the tissues.
Detailed description
Malignant gliomas are the commonest malignant brain tumors but are extremely challenging to treat. Neuro-oncology has seen little progress in its treatment despite extensive research. Extent of resection remains a very important prognostic factor in these tumors. Better the resection, better the outcomes. However resecting these tumors is not very easy primarily due to their infiltrative nature and difficulty in discerning tumor boundaries intraoperatively. Fluorescence guided resection (FGR) has recently been shown to be a very important and useful adjunct in maximizing this goal. FGR involves administration of aminolevulinic acid (ALA) to the patient prior to surgery. The ALA is converted to protoporphyrin IX (PPIX) in glioma cells. The PPIX is a fluorophore and can be visualized intraoperatively using a suitably modified microscope. Neurosurgeons can then resect the tumor radically guided by this fluorescence which is superior to the conventional microscopic resection. Selective PPIX accumulation in glioma cells is the key to the accuracy of this technique. The biological basis of selectivity of PPIX accumulation within glioma cells is however poorly understood. Various mechanisms could be involved starting from variable transport (related to blood-brain barrier properties), differential uptake (governed by active transport mechanisms) and differential metabolism within the cell. Understanding these mechanisms can lead to refinements in this strategy, overcoming its present limitations and development of methods to extend its scope.
Study design
- Observational model
- Case-control
- Time perspective
- Other
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| With ALA | – | Procedure: ALAPatients with malignant glioma. 25 patients will be provided the ALA for inducing fluorescence |
| Without ALA | – | –5 tumor tissue samples from ACTREC tumor tissue repository will be obtained. These would be malignant gliomas or other brain tumor samples where ALA is usually not administered and will be used as controls and for calibration purposes |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with malignant glioma
Key inclusion criteria (6 listed)
- Per-primum glioma
- Adults (18-65 years)
- Radiologically suspected malignant gliomas
- Variable contrast enhancement on MRI (patchy and/or non-uniform)
- Eligible for surgical therapy (craniotomy NOT stereotactic biopsy )
Key exclusion criteria (5 listed)
- Poor general condition (KPS < 70)
- Prior treatment (except biopsy)
- Compromised renal/hepatic function
- Immunocompromised status
- Known photosensitivity / allergy to 5-ALA
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 |
|---|---|---|
| ALAAlso: 5- ALAPrior to surgery all patients would receive freshly prepared solution of 5-ALA, 20 mg/kg bodyweight dissolved in 100 ml of potable water orally approximately 4 hours (range 4-6 hrs) before the commencement of anesthesia induction for surgery. The surgery would then be performed with the help of navigation. After craniotomy, the navigation software would be used to identify the selected target areas based on the preoperative images (MR as well as PET when available) and directed image-guided biopsies from these representative areas will be collected for histological evaluation | Procedure or surgery | With ALA |
Primary outcome
Degree of fluorescence
Time frame: At the time of surgery within 72 hours
1. Degree of fluorescence in different tumor regions 2. PPIX Qualification
1 secondary outcome
High throughput proteomic screening of tissue samples
Time frame: Postoperatively within 1 week of the excision
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 6 May 2022.
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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.
Aliasgar V Moiyadi, MCh DNB principal investigator
neurosurgeon
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Malignant Gliomas, run by Tata Memorial Hospital at 1 site in India.
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 6 inclusion and 5 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 6 May 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 India. 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?
Degree of fluorescence (time frame: At the time of surgery within 72 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 May 2022.