Effect of Alpha Lipoic Acid on Chemotherapy Induced Neurological Changes in Breast Cancer Patients

May 5, 2024 updated by: Shaimaa Mohamed SafaaElDin, Ain Shams University

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    * Blood samples will be withdrawn 2 times (week 1 and week 12) to measure the following: (Stored in -80 C till the end of the study)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)

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

92

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Egypt
    • El Malek El Saleh
      • Cairo, El Malek El Saleh, Egypt, 11559
        • Recruiting
        • Dar El Salam Cancer Hospital (Harmel Hospital)
        • Contact:
        • Principal Investigator:
          • Loay M Kassem, Physician

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Chemotherapy + Alpha Lipoic Acid
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).
Drug: Alpha Lipoic Acid 600 MG Oral Capsule
Single 600 mg daily dose
Other Names:
  • No drug
No Intervention: Chemotherapy only
will receive chemotherapy only (paclitaxel for 12 weeks).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tumor Necrotizing Factor Alpha Serum Levels
Time Frame: 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).
At baseline of treatment and After 12 weeks of the paclitaxel-based therapy (at the end of therapy)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response assessment by questionnaire - FACT-COG Test
Time Frame: 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.
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.
Response assessment by questionnaire - Mini-Cog Test
Time Frame: 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.
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.
Response assessment by questionnaire - Mini Mental State Examination (MMSE)
Time Frame: 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.
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.
Response assessment by questionnaire - Controlled Oral Word Association Test (COWAT)
Time Frame: 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.
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.
Response assessment by questionnaire - The Verbal Memory Arabic Test (VMAT)
Time Frame: 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.
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.
Response assessment by questionnaire - Trail Making Test (TMT)
Time Frame: 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.
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.
Brain Derived Neurotrophic Factor Serum Levels
Time Frame: 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.
At baseline and After 12 weeks of the paclitaxel-based therapy (at the end of therapy)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame: through study completion, an average of 1 year.

Monitoring alpha lipoic acid related adverse reactions:

Headache, heartburn, nausea and vomiting are nearly the most common adverse effects concerning alpha lipoic acid.
through study completion, an average of 1 year.
Monitoring the chemotherapy toxicity and side effects.
Time Frame: through study completion, an average of 1 year.
National Cancer Institute common Terminology criteria for Adverse Effect grading: NCI-CTCAE version 4.0. for evaluation of chemotherapy toxicities.
through study completion, an average of 1 year.
Monitoring Drug-Drug interactions.
Time Frame: through study completion, an average of 1 year.
Including chemotherapeutic agents and any other add-on medication.
through study completion, an average of 1 year.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ain Shams University

Collaborators

Dar EL Salam Cancer Hospital

Investigators

  • Principal Investigator: Manal H El Hamamsy, Doctorate, Ain Shams University - Faculty of Pharmacy

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2024

Primary Completion (Estimated)

April 1, 2025

Study Completion (Estimated)

April 1, 2025

Study Registration Dates

First Submitted

April 19, 2024

First Submitted That Met QC Criteria

May 5, 2024

First Posted (Actual)

May 9, 2024

Study Record Updates

Last Update Posted (Actual)

May 9, 2024

Last Update Submitted That Met QC Criteria

May 5, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RHDIRB2020110301 REC #247

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Breast Cancer

Clinical Trials on Alpha Lipoic Acid 600 MG Oral Capsule

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Finland

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe