Peripheral NeuropathyPhase 1/2NCT01313117
Alpha-lipoic Acid in Patients at Risk for Paclitaxel Induced Neuropathy
A Phase 1/2 study testing Alpha lipoic acid in people with Peripheral Neuropathy, run by Northwestern University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Peripheral Neuropathy
- What is being tested?
- Alpha lipoic acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2012to Jan 2014
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 12Show fewer
- 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.
Who cannot join
- 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
Show all 13Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Northwestern Medical Faculty Foundation
Chicago, Illinois, 60611
About this study
Official title: Dose Finding and Tolerability Study of Alpha-lipoic Acid in Patients at Risk for Paclitaxel Induced Peripheral Neuropathy
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.
- Conditions
- Peripheral Neuropathy
- Being tested
- Alpha lipoic acid
- Keywords
- chemotherapy, peripheral neuropathy, paclitaxel, breast cancer
- Medical subject headings
- Peripheral Nervous System Diseases, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alpha lipoic acidDrug
Also called Thioctic Acid
The baseline dose is 100 mg three times daily for four months. Dose escalation will occur until a maximum tolerated dose is found.
| Study group | Role | What they receive |
|---|---|---|
| Alpha lipoic acid | Experimental | Oral administration three times daily (morning, mid-day, night) Receives: Drug: Alpha lipoic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 months
Secondary outcomes (3)
Proportion of Patients Who Complete the Proposed Regimen of Daily ALA
Measured: 4 months
Cumulative Rate of Adverse Events
Measured: 4 months
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.
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2011 (estimated)
- Study startFeb 2012
- Primary completionAug 2013
- Study completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Peripheral NeuropathyStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jeffrey Allen, Northwestern University
- Investigators
- Jeffrey A. Allen, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01313117
- Sponsor's protocol ID
- NUALA-01
- Status last verified
- Sep 2014
- First submitted
- 9 Mar 2011
- Last updated
- 2 Oct 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 16797537McCarty 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.
PubMed 18789599Melli 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.
PubMed 18809400Ziegler 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.
PubMed 17065669Cremer 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.
PubMed 16904799Segermann 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.
PubMed 1815532GAL 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.
PubMed 13825981Cremer 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.
PubMed 16899332Ziegler 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.
PubMed 8786016Reljanovic 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.
PubMed 10499773Ziegler 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.
PubMed 10480774Ruhnau 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.
PubMed 10656234Ametov 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.
PubMed 12610036
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose Finding and Tolerability Study of Alpha-lipoic Acid in Patients at Risk for Paclitaxel Induced Peripheral Neuropathy
- ClinicalTrials.gov ID
- NCT01313117
- Acronym / sponsor ID
- NUALA-01
- Conditions
- Peripheral Neuropathy
- Keywords
- chemotherapy, peripheral neuropathy, paclitaxel, breast cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Study start
- Feb 2012
- Primary completion
- Aug 2013 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 11 Mar 2011 (estimated)
- Results
- Posted 2 Oct 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Alpha lipoic acid | Experimental | Drug: Alpha lipoic acidOral administration three times daily (morning, mid-day, night) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Diagnosis of Breast cancer.
- Breast cancer must meet the following criteria:
- 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
Key exclusion criteria (13 listed)
- Breast cancer meeting the following criteria:
- 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.
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 |
|---|---|---|
| Alpha lipoic acidAlso: Thioctic AcidThe baseline dose is 100 mg three times daily for four months. Dose escalation will occur until a maximum tolerated dose is found. | Drug | Alpha lipoic acid |
Primary outcome
Identification of the Optimal Dose of ALA Based on Acceptable Adverse Event(AE) Profile
Time frame: 4 months
Based on acceptable adverse event (AE) profile and continual reassessment method dose escalation.
3 secondary outcomes
Proportion of Patients Who Complete the Proposed Regimen of Daily ALA
Time frame: 4 months
Cumulative Rate of Adverse Events
Time frame: 4 months
Total Neuropathy Score (TNS)
Time frame: 4 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16797537Siau 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.
- Background: PubMed 18789599McCarty 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.
- Background: PubMed 18809400Melli 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.
- Background: PubMed 17065669Ziegler 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.
- Background: PubMed 16904799Cremer 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.
- Background: PubMed 1815532Segermann 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.
- Background: PubMed 13825981GAL 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.
- Background: PubMed 16899332Cremer 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.
- Background: PubMed 8786016Ziegler 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.
- Background: PubMed 10499773Reljanovic 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.
- Background: PubMed 10480774Ziegler 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.
- Background: PubMed 10656234Ruhnau 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.
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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.
Jeffrey A. Allen, MD principal investigator
Northwestern University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Alpha lipoic acid in people with Peripheral Neuropathy, run by Northwestern University at 1 site in United States.
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 12 inclusion and 13 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 2 Oct 2014. 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 United States. 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Oct 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Identification of the Optimal Dose of ALA Based on Acceptable Adverse Event(AE) Profile (time frame: 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01313117, which also lists 13 linked publications.
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 2 Oct 2014.