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

NCT ID: NCT01313117

Last Updated: 2014-10-02

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

9 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-02-29

Study Completion Date

2014-01-31

Brief Summary

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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.

Detailed Description

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Conditions

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Peripheral Neuropathy

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Alpha lipoic acid

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

Group Type EXPERIMENTAL

Alpha lipoic acid

Intervention Type DRUG

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

Interventions

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Alpha lipoic acid

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

Intervention Type DRUG

Other Intervention Names

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Thioctic Acid

Eligibility Criteria

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Inclusion Criteria

1. Diagnosis of Breast cancer.
2. 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)
3. Must be receiving single agent paclitaxel in their prescribed chemotherapy regimen.
4. Age \> 18 years. There is no upper age limit for participation in this study.
5. Required lab values: AST, ALT, creatinine
6. Women of childbearing potential and sexually active males must agree to use contraception while on study.
7. ECOG performance status 0,1,2
8. All patients must have given signed, informed consent.

Exclusion Criteria

1. 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
2. Evidence of pre-existing peripheral neuropathy as determined by baseline Michigan neuropathy screening instrument score \> 2.
3. Previous chemotherapy treatment of any kind.
4. AST and ALT \>2 times upper limit of normal; Creatinine \> 2.0 mg/dL.
5. Current use of medications or substances known to be associated with peripheral neuropathy.
6. Use of ALA or other anti-oxidant supplements during the prior three months.
7. Diabetes mellitus or use of medications known to lower blood sugar.
8. Participation in any other experimental trial.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Northwestern University

OTHER

Sponsor Role lead

Responsible Party

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Jeffrey Allen

Assistant Professor in Ken and Ruth Davee Department of Neurology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jeffrey A. Allen, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

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Northwestern Medical Faculty Foundation

Chicago, Illinois, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 16797537 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18789599 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18809400 (View on PubMed)

Ziegler D, Ametov A, Barinov A, Dyck PJ, Gurieva I, Low PA, Munzel U, Yakhno N, Raz I, Novosadova M, Maus J, Samigullin R. Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. Diabetes Care. 2006 Nov;29(11):2365-70. doi: 10.2337/dc06-1216.

Reference Type BACKGROUND
PMID: 17065669 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16904799 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 1815532 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 13825981 (View on PubMed)

Cremer DR, Rabeler R, Roberts A, Lynch B. Long-term safety of alpha-lipoic acid (ALA) consumption: A 2-year study. Regul Toxicol Pharmacol. 2006 Dec;46(3):193-201. doi: 10.1016/j.yrtph.2006.06.003. Epub 2006 Aug 8.

Reference Type BACKGROUND
PMID: 16899332 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8786016 (View on PubMed)

Reljanovic M, Reichel G, Rett K, Lobisch M, Schuette K, Moller W, Tritschler HJ, Mehnert H. Treatment of diabetic polyneuropathy with the antioxidant thioctic acid (alpha-lipoic acid): a two year multicenter randomized double-blind placebo-controlled trial (ALADIN II). Alpha Lipoic Acid in Diabetic Neuropathy. Free Radic Res. 1999 Sep;31(3):171-9. doi: 10.1080/10715769900300721.

Reference Type BACKGROUND
PMID: 10499773 (View on PubMed)

Ziegler D, Hanefeld M, Ruhnau KJ, Hasche H, Lobisch M, Schutte K, Kerum G, Malessa R. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III Study). ALADIN III Study Group. Alpha-Lipoic Acid in Diabetic Neuropathy. Diabetes Care. 1999 Aug;22(8):1296-301. doi: 10.2337/diacare.22.8.1296.

Reference Type BACKGROUND
PMID: 10480774 (View on PubMed)

Ruhnau KJ, Meissner HP, Finn JR, Reljanovic M, Lobisch M, Schutte K, Nehrdich D, Tritschler HJ, Mehnert H, Ziegler D. Effects of 3-week oral treatment with the antioxidant thioctic acid (alpha-lipoic acid) in symptomatic diabetic polyneuropathy. Diabet Med. 1999 Dec;16(12):1040-3. doi: 10.1046/j.1464-5491.1999.00190.x.

Reference Type BACKGROUND
PMID: 10656234 (View on PubMed)

Ametov AS, Barinov A, Dyck PJ, Hermann R, Kozlova N, Litchy WJ, Low PA, Nehrdich D, Novosadova M, O'Brien PC, Reljanovic M, Samigullin R, Schuette K, Strokov I, Tritschler HJ, Wessel K, Yakhno N, Ziegler D; SYDNEY Trial Study Group. The sensory symptoms of diabetic polyneuropathy are improved with alpha-lipoic acid: the SYDNEY trial. Diabetes Care. 2003 Mar;26(3):770-6. doi: 10.2337/diacare.26.3.770.

Reference Type BACKGROUND
PMID: 12610036 (View on PubMed)

Other Identifiers

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NUALA-01

Identifier Type: -

Identifier Source: org_study_id

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