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Lipoic Acid Supplement for Cystine Stone (ALA)

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ClinicalTrials.gov Identifier: NCT02910531
Recruitment Status : Recruiting
First Posted : September 22, 2016
Last Update Posted : April 17, 2019
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
University of California, San Francisco

Tracking Information
First Submitted Date  ICMJE September 20, 2016
First Posted Date  ICMJE September 22, 2016
Last Update Posted Date April 17, 2019
Actual Study Start Date  ICMJE June 19, 2017
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 20, 2016)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02910531 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 20, 2016)
Urinary cystine level [ Time Frame: 3 years ]
The secondary endpoints will be quantitative urinary cystine level determined by 24-hour urine collection.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Lipoic Acid Supplement for Cystine Stone
Official Title  ICMJE The Effect of Lipoic Acid Natural Supplement on Cystine Stone Formation
Brief 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Cystinuria
Intervention  ICMJE
  • Dietary Supplement: Alpha lipoic acid
    Already mentioned in arm/group descriptions.
  • Drug: Placebo
    Already mentioned in arm/group descriptions.
Study Arms  ICMJE
  • 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.

    Intervention: Dietary Supplement: Alpha lipoic acid
  • 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.

    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 20, 2016)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2023
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Thomas Chi, MD 415-206-2934 tom.chi@ucsf.edu
Contact: Victoria Hogue, MA Victoria.Hogue@ucsf.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02910531
Other Study ID Numbers  ICMJE 16-20523
2P20DK100863-03 ( U.S. NIH Grant/Contract )
OPD Grant Number 5716 ( Other Grant/Funding Number: US Food and Drug Administration )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of California, San Francisco
Study Sponsor  ICMJE University of California, San Francisco
Collaborators  ICMJE National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators  ICMJE
Principal Investigator: Thomas Chi, MD University of California, San Francisco
PRS Account University of California, San Francisco
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP