Lipoic Acid Supplement for Cystine Stone

Cystinuria Clinical Trial

— ALA  

Official title:

The Effect of Lipoic Acid Natural Supplement on Cystine Stone Formation

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02910531
• Other study ID #: 16-20523
• Secondary ID: 2P20DK100863-03O
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 19, 2017
• Est. completion date: June 2025

Study information

• Verified date: December 2023
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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 (Chillarón 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: June 2025
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cystinuria

Intervention

Dietary Supplement:
• Alpha lipoic acid
Already mentioned in arm/group descriptions.

Drug:
• Placebo
Already mentioned in arm/group descriptions.

Locations

Country	Name	City	State
United States	University of California, San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Thomas Chi, MD	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cystine stone recurrence	The primary efficacy endpoint will be assessed in two ways: symptomatic stone recurrences, defined as renal colic, stone passage, or surgical removal of a stone; silent stone recurrences, classified as stone growth or new stones, diagnosed on the basis of renal ultrasound, plain KUB x-ray, or if clinically indicated, computed tomography.	3 years
Secondary	Urinary cystine level	The secondary endpoints will be quantitative urinary cystine level determined by 24-hour urine collection.	3 years