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Lipoic Acid Supplement for Cystine Stone (ALA)

This study is currently recruiting participants.
See Contacts and Locations
Verified July 2017 by University of California, San Francisco
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT02910531
First received: September 20, 2016
Last updated: July 18, 2017
Last verified: July 2017
  Purpose
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.

Condition Intervention Phase
Cystinuria Dietary Supplement: Alpha lipoic acid Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: The Effect of Lipoic Acid Natural Supplement on Cystine Stone Formation

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • Urinary cystine level [ Time Frame: 3 years ]
    The secondary endpoints will be quantitative urinary cystine level determined by 24-hour urine collection.


Estimated Enrollment: 50
Actual Study Start Date: June 19, 2017
Estimated Study Completion Date: May 2022
Estimated Primary Completion Date: May 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02910531

Contacts
Contact: Thomas Chi, MD 415-206-2934 tom.chi@ucsf.edu
Contact: Victoria Hogue, MA Victoria.Hogue@ucsf.edu

Locations
United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Sponsors and Collaborators
University of California, San Francisco
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Principal Investigator: Thomas Chi, MD University of California, San Francisco
  More Information

Publications:
Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT02910531     History of Changes
Other Study ID Numbers: 16-20523
2P20DK100863-03 ( U.S. NIH Grant/Contract )
Study First Received: September 20, 2016
Last Updated: July 18, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of California, San Francisco:
Cystinuria
Kidney stone
Alpha lipoic acid

Additional relevant MeSH terms:
Cystinuria
Renal Aminoacidurias
Renal Tubular Transport, Inborn Errors
Kidney Diseases
Urologic Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Thioctic Acid
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on September 19, 2017