Lipoic Acid Supplement for Cystine Stone

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.

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.