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Alpha-lipoic Acid in Patients at Risk for Paclitaxel Induced Neuropathy

Primary Purpose

Peripheral Neuropathy

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Alpha lipoic acid

About this trial

This is an interventional treatment trial for Peripheral Neuropathy focused on measuring chemotherapy, peripheral neuropathy, paclitaxel, breast cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria

Diagnosis of Breast cancer.
Breast cancer must meet the following criteria:
- Early stage breast cancer (stages I, IIA) must be estrogen receptor (ER) positive AND low tumor grade (histopathologic grade 1 or 2)
- Locally advanced breast cancer (LABC) (stages IIB, IIIA, IIB as defined by the Union for International Cancer Control and American Joint Committee on Cancer) must be ER positive, HER2 positive or HER2 negative, AND satisfy the following requirements: high endocrine responsiveness (defined as greater than 50% of tumor cells staining for hormone receptors), Grade 1 or 2 histological grade, less than 4 nodes positive, absence of extensive peritumoral vascular invasion, AND pathological tumor size less than 5 cm.
- Inflammatory breast cancer (IBC) (stage IIIC)
- Metastatic breast cancer (stage IV)
Must be receiving single agent paclitaxel in their prescribed chemotherapy regimen.
Age > 18 years. There is no upper age limit for participation in this study.
Required lab values: AST, ALT, creatinine
Women of childbearing potential and sexually active males must agree to use contraception while on study.
ECOG performance status 0,1,2
All patients must have given signed, informed consent.

Exclusion Criteria

Breast cancer meeting the following criteria:
- Breast cancer stage 0
- Early stage breast cancer (stages I, IIA) that is ER negative OR higher tumor grade (histopathologic grade greater than 2)
- Stages I, II, and IIIA triple negative breast cancer (negative for estrogen receptors, progesterone receptors, and HER2)
- LABC (stages IIB, IIIA, IIB) if they have low endocrine responsiveness (defined as less than 50% of tumor cells staining for hormone receptors), Grade 3 histological grade, 4 or more nodes positive, presence of extensive peritumoral vascular invasion, OR pathological tumor size greater than 5 cm
- LABC (stages IIB, IIIA, IIB) that are ER negative
Evidence of pre-existing peripheral neuropathy as determined by baseline Michigan neuropathy screening instrument score > 2.
Previous chemotherapy treatment of any kind.
AST and ALT >2 times upper limit of normal; Creatinine > 2.0 mg/dL.
Current use of medications or substances known to be associated with peripheral neuropathy.
Use of ALA or other anti-oxidant supplements during the prior three months.
Diabetes mellitus or use of medications known to lower blood sugar.
Participation in any other experimental trial.

Sites / Locations

Northwestern Medical Faculty Foundation

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Alpha lipoic acid

Arm Description

Oral administration three times daily (morning, mid-day, night)

Outcomes

Primary Outcome Measures

Identification of the Optimal Dose of ALA Based on Acceptable Adverse Event(AE) Profile

Based on acceptable adverse event (AE) profile and continual reassessment method dose escalation.

Secondary Outcome Measures

Proportion of Patients Who Complete the Proposed Regimen of Daily ALA

Cumulative Rate of Adverse Events

Total Neuropathy Score (TNS)

The Total Neuropathy score (TNS) is a validated score that combines signs, symptoms, and very limited nerve conduction studies (NCS). It was designed to assess peripheral nerve function and has been used as an endpoint in clinical trials of toxic neuropathy. The TNS is a composite scale with a range of values from 0 (normal) to 28 (severely affected). It includes data from 7 different categories. Patients are asked to assess the severity of sensory symptoms on a scale of 0 (no symptoms) to 4 (symptoms above knees or elbows, or functionally disabling). Next, 4 examination categories are assessed. These include pin sensation, vibration sensation, deep tendon reflexes, and strength. Signs are scored from 0 to 4 depending on severity. The nerve conduction portion of the scale consists of measurements of a motor (peroneal) and sensory (sural) nerve. Motor and sensory responses are graded on a scale of 0 to 4 depending on the severity of an abnormality.

Full Information

NCT ID

NCT01313117

First Posted

March 9, 2011

Last Updated

September 26, 2014

Sponsor

Northwestern University

1. Study Identification

Unique Protocol Identification Number

NCT01313117

Brief Title

Alpha-lipoic Acid in Patients at Risk for Paclitaxel Induced Neuropathy

Official Title

Dose Finding and Tolerability Study of Alpha-lipoic Acid in Patients at Risk for Paclitaxel Induced Peripheral Neuropathy

Study Type

Interventional

2. Study Status

Record Verification Date

September 2014

Overall Recruitment Status

Completed

Study Start Date

February 2012 (undefined)

Primary Completion Date

August 2013 (Actual)

Study Completion Date

January 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Northwestern University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This study is being done because peripheral neuropathy, a condition that interrupts sensation in your limbs, is a common side effect of paclitaxel. There is some evidence that alpha lipoic acid (ALA), an antioxidant compound, protects neurons after exposure to paclitaxel. The purpose of this study is to assess the safety and tolerability of ALA and to find the best dose of ALA in patients that receive chemotherapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Peripheral Neuropathy

Keywords

chemotherapy, peripheral neuropathy, paclitaxel, breast cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Alpha lipoic acid

Arm Type

Experimental

Arm Description

Oral administration three times daily (morning, mid-day, night)

Intervention Type

Drug

Intervention Name(s)

Alpha lipoic acid

Other Intervention Name(s)

Thioctic Acid

Intervention Description

The baseline dose is 100 mg three times daily for four months. Dose escalation will occur until a maximum tolerated dose is found.

Primary Outcome Measure Information:

Title

Identification of the Optimal Dose of ALA Based on Acceptable Adverse Event(AE) Profile

Description

Based on acceptable adverse event (AE) profile and continual reassessment method dose escalation.

Time Frame

4 months

Secondary Outcome Measure Information:

Title

Proportion of Patients Who Complete the Proposed Regimen of Daily ALA

Time Frame

4 months

Title

Cumulative Rate of Adverse Events

Time Frame

4 months

Title

Total Neuropathy Score (TNS)

Description

Time Frame

4 months

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria Diagnosis of Breast cancer. Breast cancer must meet the following criteria: Early stage breast cancer (stages I, IIA) must be estrogen receptor (ER) positive AND low tumor grade (histopathologic grade 1 or 2) Locally advanced breast cancer (LABC) (stages IIB, IIIA, IIB as defined by the Union for International Cancer Control and American Joint Committee on Cancer) must be ER positive, HER2 positive or HER2 negative, AND satisfy the following requirements: high endocrine responsiveness (defined as greater than 50% of tumor cells staining for hormone receptors), Grade 1 or 2 histological grade, less than 4 nodes positive, absence of extensive peritumoral vascular invasion, AND pathological tumor size less than 5 cm. Inflammatory breast cancer (IBC) (stage IIIC) Metastatic breast cancer (stage IV) Must be receiving single agent paclitaxel in their prescribed chemotherapy regimen. Age > 18 years. There is no upper age limit for participation in this study. Required lab values: AST, ALT, creatinine Women of childbearing potential and sexually active males must agree to use contraception while on study. ECOG performance status 0,1,2 All patients must have given signed, informed consent. Exclusion Criteria Breast cancer meeting the following criteria: Breast cancer stage 0 Early stage breast cancer (stages I, IIA) that is ER negative OR higher tumor grade (histopathologic grade greater than 2) Stages I, II, and IIIA triple negative breast cancer (negative for estrogen receptors, progesterone receptors, and HER2) LABC (stages IIB, IIIA, IIB) if they have low endocrine responsiveness (defined as less than 50% of tumor cells staining for hormone receptors), Grade 3 histological grade, 4 or more nodes positive, presence of extensive peritumoral vascular invasion, OR pathological tumor size greater than 5 cm LABC (stages IIB, IIIA, IIB) that are ER negative Evidence of pre-existing peripheral neuropathy as determined by baseline Michigan neuropathy screening instrument score > 2. Previous chemotherapy treatment of any kind. AST and ALT >2 times upper limit of normal; Creatinine > 2.0 mg/dL. Current use of medications or substances known to be associated with peripheral neuropathy. Use of ALA or other anti-oxidant supplements during the prior three months. Diabetes mellitus or use of medications known to lower blood sugar. Participation in any other experimental trial.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jeffrey A. Allen, MD

Organizational Affiliation

Northwestern University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Northwestern Medical Faculty Foundation

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

16797537

Citation

Siau C, Xiao W, Bennett GJ. Paclitaxel- and vincristine-evoked painful peripheral neuropathies: loss of epidermal innervation and activation of Langerhans cells. Exp Neurol. 2006 Oct;201(2):507-14. doi: 10.1016/j.expneurol.2006.05.007. Epub 2006 Jun 22.

Results Reference

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18789599

Citation

McCarty MF, Barroso-Aranda J, Contreras F. The "rejuvenatory" impact of lipoic acid on mitochondrial function in aging rats may reflect induction and activation of PPAR-gamma coactivator-1alpha. Med Hypotheses. 2009 Jan;72(1):29-33. doi: 10.1016/j.mehy.2008.07.043. Epub 2008 Sep 11.

Results Reference

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PubMed Identifier

18809400

Citation

Melli G, Taiana M, Camozzi F, Triolo D, Podini P, Quattrini A, Taroni F, Lauria G. Alpha-lipoic acid prevents mitochondrial damage and neurotoxicity in experimental chemotherapy neuropathy. Exp Neurol. 2008 Dec;214(2):276-84. doi: 10.1016/j.expneurol.2008.08.013. Epub 2008 Sep 9.

Results Reference

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PubMed Identifier

17065669

Citation

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PubMed Identifier

16904799

Citation

Cremer DR, Rabeler R, Roberts A, Lynch B. Safety evaluation of alpha-lipoic acid (ALA). Regul Toxicol Pharmacol. 2006 Oct;46(1):29-41. doi: 10.1016/j.yrtph.2006.06.004. Epub 2006 Aug 14.

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PubMed Identifier

1815532

Citation

Segermann J, Hotze A, Ulrich H, Rao GS. Effect of alpha-lipoic acid on the peripheral conversion of thyroxine to triiodothyronine and on serum lipid-, protein- and glucose levels. Arzneimittelforschung. 1991 Dec;41(12):1294-8.

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PubMed Identifier

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Citation

GAL EM, RAZEVSKA DE. Studies on the in vivo metabolism of lipoic acid. 1. The fate of DL-lipoic acid-S35 in normal and thiamine-deficient rats. Arch Biochem Biophys. 1960 Aug;89:253-61. doi: 10.1016/0003-9861(60)90051-5. No abstract available.

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Citation

Ziegler D, Hanefeld M, Ruhnau KJ, Meissner HP, Lobisch M, Schutte K, Gries FA. Treatment of symptomatic diabetic peripheral neuropathy with the anti-oxidant alpha-lipoic acid. A 3-week multicentre randomized controlled trial (ALADIN Study). Diabetologia. 1995 Dec;38(12):1425-33. doi: 10.1007/BF00400603.

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Alpha-lipoic Acid in Patients at Risk for Paclitaxel Induced Neuropathy

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