Lipoic Acid Supplement for Cystine Stone

NCT ID: NCT02910531

Last Updated: 2023-12-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-06-19

Study Completion Date

2025-06-30

Brief Summary

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This study evaluates how daily alpha lipoic acid supplementation affects cystine kidney stone recurrence. Half of the subjects will receive 1200 mg alpha lipoic acid orally daily for three years, while the other half will receive a placebo. The funding source for this clinical trial is FDA OOPD.

Detailed Description

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Cystinuria is a rare inherited autosomal recessive disorder of the kidney that is the result of a defect in the dibasic amino acid transporter in the renal proximal tubule and small intestine. Supersaturation of cystine in the urine produces crystals that precipitate and form calculi, which can be a cause of obstruction, infection, and chronic kidney disease (ChillarĂ³n 2010).

One potential therapeutic is a thiol-containing compound alpha-lipoic acid (thioctic acid, 5-(1,2-dithiolan-3- yl) pentanoic acid, ALA). It is an over-the-counter supplement with antioxidant property. Once ALA is transported into the cell, it is reduced to dihydrolipoic acid (DHLA). Both ALA and DHLA have direct antioxidant activity (Scholich 1989), and they can regenerate endogenous antioxidants including ascorbic acid and vitamin E. It can also increase intracellular coenzyme Q10 and glutathione levels. ALA and DHLA also have additional biochemical effects as metal chelators, reactive oxygen species scavengers, and modulators of signaling transduction of several pathways (Gomes 2014).

While the potential therapeutic effects of ALA have been studied in a number of diseases including, for example, Alzheimer's disease, obesity, cardiovascular disease, hypertension, and several cancers (Gomes 2014), the efficacy of ALA has been best studied in type 2 diabetic peripheral neuropathy (Ziegler 2011). In our lab, results from a mouse model of cystinuria show that ALA markedly slows the initiation of cystine stone formation as well as the growth of existing stones.

Given this history in clinical medicine and, most importantly, based upon our positive findings of ALA effectiveness in a mouse model of cystinuria, we propose a pilot study on the use of this molecule in cystinuric patients.

Conditions

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Cystinuria

Keywords

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Cystinuria Kidney stone Alpha lipoic acid

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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ALA supplement

Clinical data including medical history, plain KUB x-ray and renal ultrasound, routine blood work and 24-hour urine collections for all subjects will be collected as part of normal clinical care at routine clinical visit every 4 months.

Subjects in this study arm will be taking one supplement tablet containing 1200 mg of alpha lipoic acid orally once daily for three years.

At the end of the three years of study drug treatment, all subjects will undergo a low dose non-contrast CT scan to look for a silent change in stone size.

Group Type EXPERIMENTAL

Alpha lipoic acid

Intervention Type DIETARY_SUPPLEMENT

Already mentioned in arm/group descriptions.

Placebo

Clinical data including medical history, plain KUB x-ray and renal ultrasound, routine blood work and 24-hour urine collections for all subjects will be collected as part of normal clinical care at routine clinical visit every 4 months.

Subjects in this study arm will be taking one placebo tablet containing 10 mg of sucrose orally once daily for three years.

At the end of the three years of study drug treatment, all subjects will undergo a low dose non-contrast CT scan to look for a silent change in stone size.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Already mentioned in arm/group descriptions.

Interventions

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Alpha lipoic acid

Already mentioned in arm/group descriptions.

Intervention Type DIETARY_SUPPLEMENT

Placebo

Already mentioned in arm/group descriptions.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Documented cystinuria on prior 24-hour urine collection and/or stone analysis; history of previous cystine kidney stones.
* Being able and willing to provide consent.

Exclusion Criteria

* Poorly controlled diabetes mellitus (hemoglobin A1C \> 8.0% for more than 1 year).
* Current alpha-lipoic acid administration at the time of screening or within the last year prior to screening.
* Vulnerable populations including incarceration status.
* Unable to give informed consent.
* Non-English primary language.
* Pregnancy, lactation, or child-bearing age without birth control devices.
* Anticipation of pregnancy during the study period.
* Serious illness likely to cause death within the next 5 years.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role collaborator

Thomas Chi, MD

OTHER

Sponsor Role lead

Responsible Party

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Thomas Chi, MD

Professor, Urology

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Thomas Chi, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

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University of California, San Francisco

San Francisco, California, United States

Site Status

Countries

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United States

References

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Chillaron J, Font-Llitjos M, Fort J, Zorzano A, Goldfarb DS, Nunes V, Palacin M. Pathophysiology and treatment of cystinuria. Nat Rev Nephrol. 2010 Jul;6(7):424-34. doi: 10.1038/nrneph.2010.69. Epub 2010 Jun 1.

Reference Type BACKGROUND
PMID: 20517292 (View on PubMed)

Gomes MB, Negrato CA. Alpha-lipoic acid as a pleiotropic compound with potential therapeutic use in diabetes and other chronic diseases. Diabetol Metab Syndr. 2014 Jul 28;6(1):80. doi: 10.1186/1758-5996-6-80. eCollection 2014.

Reference Type BACKGROUND
PMID: 25104975 (View on PubMed)

Ziegler D, Low PA, Litchy WJ, Boulton AJ, Vinik AI, Freeman R, Samigullin R, Tritschler H, Munzel U, Maus J, Schutte K, Dyck PJ. Efficacy and safety of antioxidant treatment with alpha-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. Diabetes Care. 2011 Sep;34(9):2054-60. doi: 10.2337/dc11-0503. Epub 2011 Jul 20.

Reference Type BACKGROUND
PMID: 21775755 (View on PubMed)

Scholich H, Murphy ME, Sies H. Antioxidant activity of dihydrolipoate against microsomal lipid peroxidation and its dependence on alpha-tocopherol. Biochim Biophys Acta. 1989 Feb 20;1001(3):256-61. doi: 10.1016/0005-2760(89)90108-2.

Reference Type BACKGROUND
PMID: 2492825 (View on PubMed)

Other Identifiers

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2P20DK100863-03

Identifier Type: NIH

Identifier Source: secondary_id

View Link

OPD Grant Number 5716

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

16-20523

Identifier Type: -

Identifier Source: org_study_id