Effect of Alpha Lipoic Acid on Chemotherapy Induced Neurological Changes in Breast Cancer Patients
- Conditions
- Breast CancerAlpha Lipoic AcidPaclitaxelNeurologic DisorderChemotherapy
- Interventions
- Drug: Alpha Lipoic Acid 600 MG Oral Capsule
- Registration Number
- NCT06406127
- Lead Sponsor
- Ain Shams University
- Brief Summary
92 female cancer patients, aged from 18 to 75 years old (with a first diagnosis of breast cancer) who will receive Paclitaxel-based chemotherapy (12 weeks) as first line therapy, will be enrolled in the study and will be randomly assigned to either:
* Group I: will receive the chemotherapy protocol or
* Group II: will receive the chemotherapy protocol plus 600 mg daily dose of Alpha Lipoic Acid for 14 weeks (one week before the start of paclitaxel and continue till one week after the end of paclitaxel).
\* Blood samples will be withdrawn 2 times (week 1 and week 12) to measure the following: (Stored in -80 C till the end of the study)
* Tumor Necrotizing Factor- alpha (TNF-α) by ELISA.
* Brain-Derived Neurotrophic Factor (BDNF) by ELISA.
\* All patients will be subjected to 6 tests/questionnaires (week 1 - week 12 - week 24) to predict the functionality of the brain:
* Functional Assessment of Cancer Therapy-Cognitive (FACT-Cog) version 3
* Mini-Cog Test
* Mini Mental State Examination (MMSE)
* Controlled Oral Word Association Test (COWAT)
* Hopkins Verbal Learning Test (HVLT)
* Trail Making Test (TMT)
- Detailed Description
92 Female Cancer patients will be randomized to 2 groups, the first group will receive the alpha lipoic acid beside their chemotherapy regimen and the other group will only receive the chemotherapy regimen. Both groups will be watched for any changes in their neurological behaviors by asking and receiving answers on the questionnaires that were mentioned before. This will be done in 3 different time margins:
* Before starting the chemotherapeutic regimen
* after ending the chemotherapeutic regimen
* after 6 months of receiving the chemotherapeutic regimen this will show even the late symptoms and effects of the chemotherapy. Also serum biomarkers will be measured (TNF alpha and BDNF) 2 times; one before starting the chemotherapeutic regimen and the other after ending the treatment.
Throughout the treatment process, both groups will be monitored for any side effects concerning the alpha lipoic acid or the chemotherapeutic regimen.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 92
- Female breast cancer patients aged 18 to 75 years old.
- Patients with a first diagnosis of cancer and indication for first-line therapy with Paclitaxel-based chemotherapy.
- Patients are those who are diagnosed with Stage 1 to 3 non-metastatic breast cancer.
- Patients are intended to receive 12 weeks of paclitaxel (75 - 80 mg/m2) according to the TC protocol.
- No previous neurological conditions (including dementia, Alzheimer's disease, Parkinson's disease) and taking no neurological-related drugs.
- Normal hepatic and renal function (bilirubin ≤1.5 mg/dL, creatinine ≤2.0 mg/dL).
- Eastern Cooperative Oncology Group (ECOG) performance status from 0 - 2.
- Patient Health Questionnaire (PHQ) score from 0 - 9.
- Hypersensitivity / Allergy to Alpha Lipoic Acid.
- Any condition that contraindicates chemotherapy (i.e., pregnancy, lactation).
- New-onset neurological symptoms or presence of any neurological disorder.
- Patients with known history or current treatment with neurological agents.
- Alcohol abuse.
- Current participation in any other clinical investigation.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Chemotherapy + Alpha Lipoic Acid Alpha Lipoic Acid 600 MG Oral Capsule will receive chemotherapy (paclitaxel for 12 weeks) + Alpha Lipoic Acid for 14 weeks (one week before the start of paclitaxel and continue for one week after the end of paclitaxel).
- Primary Outcome Measures
Name Time Method Tumor Necrotizing Factor Alpha Serum Levels At baseline of treatment and After 12 weeks of the paclitaxel-based therapy (at the end of therapy) All patients will be evaluated during the trial for 2 times via monitoring the Tumor Necrotizing Factor- alpha (TNF-α).
- Secondary Outcome Measures
Name Time Method Response assessment by questionnaire - FACT-COG Test For 3 times during the study: - At baseline - After 12 weeks of the paclitaxel-based therapy. - After 6 months from the start of the paclitaxel-based therapy. Evaluation of response will be done guided by the questionnaire to detect the neuropsychiatric panel.
FACT Cognitive function version 3 consists of questions regarding:
* Perceived cognitive impairments.
* Comments from others.
* Perceived cognitive abilities.
* Impact on quality of life. For every answered question, the patient receives points on a scale of scores. Those scales will be compared in every time the questionnaire is conducted to assess the functionality of the brain.
The scale of numbers of the answers is:
* Never = 0
* About once a week = 1
* Two to three times a week = 2
* Nearly every day = 3
* Several times a day = 4 It is better when the patient has low score.Response assessment by questionnaire - The Verbal Memory Arabic Test (VMAT) For 3 times during the study: - At baseline - After 12 weeks of the paclitaxel-based therapy. - After 6 months from the start of the paclitaxel-based therapy. Evaluation of response will be done guided by the questionnaire to detect the neuropsychiatric panel.
The VMAT consists of 3 trials of delayed recall. Every trial has a list of words for which the patient will be asked to recall. For every recalled word the patient will have a point and those points will be compared in every time the questionnaire is conducted to assess the functionality of the brain.
The more words recalled, the better.Response assessment by questionnaire - Mini-Cog Test For 3 times during the study: - At baseline - After 12 weeks of the paclitaxel-based therapy. - After 6 months from the start of the paclitaxel-based therapy. Evaluation of response will be done guided by the questionnaire to detect the neuropsychiatric panel.
Mini-Cog Test consists of three steps:
* Three Word Registration: Telling the patient a list of words and ask him to memorize them.
* Clock Drawing: Asking the patient to draw the clock and record the time taken for drawing. Normal clock = 2 points. Inability or refusal to draw a clock (abnormal) = 0 points.
* Three-Word Recall: Asking the patient to recall the list of words done in step 1.
For every word recalled, patient receives a point. Total points will be compared in every time the questionnaire is done to assess the functionality of the brain.Response assessment by questionnaire - Mini Mental State Examination (MMSE) For 3 times during the study: - At baseline - After 12 weeks of the paclitaxel-based therapy. - After 6 months from the start of the paclitaxel-based therapy. Evaluation of response will be done guided by the questionnaire to detect the neuropsychiatric panel.
MMSE consists of questions regarding:
* Orientation to time (2 points, one for each question)
* Orientation to place (2 points, one for each question)
* Concentration and attention (2 questions and for each question this scale will be applied: No Errors - 2 points, 1 Error - 1 point, 2 or more Errors - 0 points)
* Delayed recall (3 points, one for each recalled word) For every answered question, the patient will get points. Those points will be compared in every phase the questionnaire is done for every patient.Response assessment by questionnaire - Controlled Oral Word Association Test (COWAT) For 3 times during the study: - At baseline - After 12 weeks of the paclitaxel-based therapy. - After 6 months from the start of the paclitaxel-based therapy. Evaluation of response will be done guided by the questionnaire to detect the neuropsychiatric panel.
The patient is asked to tell words that begin with a certain alphabet in a certain time margin. This will be done for 4 different alphabets and words will be recorded to calculate the score.
Points of every alphabet will be compared in every time the questionnaire is conducted to assess the functionality of the brain.
The more words told in the same time margin, the better.Brain Derived Neurotrophic Factor Serum Levels At baseline and After 12 weeks of the paclitaxel-based therapy (at the end of therapy) All patients will be evaluated during the trial for 2 times via monitoring Brain-Derived Neurotrophic Factor (BDNF) serum levels.
Response assessment by questionnaire - Trail Making Test (TMT) For 3 times during the study: - At baseline - After 12 weeks of the paclitaxel-based therapy. - After 6 months from the start of the paclitaxel-based therapy. Evaluation of response will be done guided by the questionnaire to detect the neuropsychiatric panel.
TMT consists of 2 parts, A and B. Both parts of the Trail Making Test consist of 25 circles distributed over a sheet of paper. In Part A, the circles are numbered 1 - 25, and the patient should draw lines to connect the numbers in ascending order. In Part B, the circles include both numbers and letters; as in Part A, the patient draws lines to connect the circles in an ascending pattern, but with the added task of alternating between the numbers and letters (i.e., 1-A-2-B-3-C, etc.).
Results for both TMT A and B are reported as the number of seconds required to complete the task; therefore, higher scores reveal greater impairment.
Trial Locations
- Locations (1)
Dar El Salam Cancer Hospital (Harmel Hospital)
🇪🇬Cairo, El Malek El Saleh, Egypt