Lipoic Acid Supplement for Cystine Stone (ALA)

December 18, 2023 updated by: Thomas Chi, MD

The Effect of Lipoic Acid Natural Supplement on Cystine Stone Formation

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94143
        • University of California, San Francisco

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Dietary supplement: Alpha lipoic acid
Already mentioned in arm/group descriptions.
Placebo Comparator: 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.
Drug: Placebo
Already mentioned in arm/group descriptions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cystine stone recurrence
Time Frame: 3 years

The primary efficacy endpoint will be assessed in two ways:

  1. symptomatic stone recurrences, defined as renal colic, stone passage, or surgical removal of a stone;
  2. 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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Urinary cystine level
Time Frame: 3 years
The secondary endpoints will be quantitative urinary cystine level determined by 24-hour urine collection.
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Thomas Chi, MD

Collaborators

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

Investigators

  • Principal Investigator: Thomas Chi, MD, University of California, San Francisco

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 19, 2017

Primary Completion (Estimated)

June 1, 2024

Study Completion (Estimated)

June 1, 2025

Study Registration Dates

First Submitted

September 20, 2016

First Submitted That Met QC Criteria

September 20, 2016

First Posted (Estimated)

September 22, 2016

Study Record Updates

Last Update Posted (Estimated)

December 20, 2023

Last Update Submitted That Met QC Criteria

December 18, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 16-20523
  • 2P20DK100863-03 (U.S. NIH Grant/Contract)
  • OPD Grant Number 5716 (Other Grant/Funding Number: US Food and Drug Administration)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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