Valproic Acid-associated Hypoalbuminemia in Medically Fragile Patients

March 8, 2011 updated by: Akron Children's Hospital

Valproic Acid-associated Hypoalbuminemia in Medically Fragile Pediatric and Young Adult Patients in a Long Term Care Facility Part 1: Potential Mechanism for Decreased Albumin Synthesis

The purpose of this study is to investigate potential mechanisms of valproic acid-associated low serum albumin in medically fragile pediatric and young adult epileptic patients of a long-term care facility.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Valproic acid (VPA) is a long-chain fatty acid frequently used as an antiepileptic agent in pediatric and adult seizure patients. Other adverse effects that have been associated with VPA use include hepatic steatosis, altered mitochondrial function and decreased concentrations of serum proteins. The exact mechanism or mechanisms by which VPA induces these associated adverse drug effects are not fully understood though multiple theories have been postulated including impaired vesicle transport within the hepatocyte, inhibition of hepatic synthetic metabolic pathways and renal protein loss. Decreased serum albumin concentrations with concomitant VPA use have been identified in multiple studies. Albumin synthesis is sensitive to tryptophan concentrations (other amino acids are also able to stimulate albumin synthesis), oncotic pressure near the synthetic site, and energy supply while albumin release from the hepatocyte is sensitive to intrahepatocellular potassium concentrations. Based on available literature, VPA appears to inhibit an enzyme(s) either directly or indirectly involved with albumin synthesis or albumin gene expression. VPA is known to inhibit the urea cycle, including patients with ornithine-transcarbamylase (OTC) deficiency, possibly by inhibiting mitochondrial carbamoyl-phosphate synthase. Oratz et al discussed the potential correlation between the urea cycle and albumin synthesis identified after the administration of various amino acids increased both albumin and urea synthesis. Ornithine is an intermediate amino acid within the urea cycle and it is also a precursor to polyamines which have been shown to increase the degree of aggregation of polysomes, responsible for protein synthesis, bound to the endoplasmic reticulum. Thus, VPA may indirectly inhibit protein synthesis by interfering with the urea cycle leading to decreased ornithine concentrations and subsequently a decrease in polyamine concentrations and a decrease in the number of bound polysomes resulting in alterations in albumin synthesis and release. The purpose of this study is to investigate potential mechanisms of VPA-associated hypoalbuminemia in medically fragile pediatric and young adult epileptic patients of a long-term care facility.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
90

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
    • Ohio
      • Mantua, Ohio, United States, 44255
        • Hattie Larlham Center for Children with Disabilities

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Medically fragile residents of the Hattie Larlham Long Term Care Facilit.

Description

Inclusion Criteria:

  • Resident of Hattie Larlham long-term care facility receiving VPA for > 3 months at the start of the study
  • Resident of Hattie Larlham long-term care facility matched to a resident receiving VPA for > 3 month based on concomitant AED, length of time on AED, age, and gender
  • Resident of Hattie Larlham long-term care facility not receiving AED matched to a resident receiving VPA for > 3 month based on age and gender

Exclusion Criteria:

  • Received albumin products within the past 1 month
  • Receiving VPA for < 3 months or discontinuation of VPA therapy within the past four weeks
  • Medical need for specific protein supplementation
  • Diagnosed with protein-losing nephropathy or enteropathy

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

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
1
Resident of Hattie Larlham long-term care facility receiving VPA
Procedure: Specimen collection
A blood sample and a spot urine sample will be obtained from all eligible patients receiving VPA at the start of the study.
2
Control AED patients will be recruited based on similar AED regimens excluding VPA, length of time on AED (number of months to >1 year), age, and gender; one control patient per VPA patient.
3
Control non-AED patients will be recruited based on age and gender; one control patient per VPA patient.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
The primary outcome will be serum albumin concentrations at baseline in the patients receiving VPA.
Time Frame: Baseline
Baseline

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Secondary outcome variables will include serum amino acid concentrations, total protein, AST, ALT, alkaline phosphatase, ammonia, BUN, and sCr and urine albumin, protein, and urea.
Time Frame: Baseline
Baseline

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Akron Children's Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Michael Reed, PharmD, Akron Children's Hospital Research Center
  • Study Chair: Richard Grossberg, MD, Hattie Larlham

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2009

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2009

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2010

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 25, 2008

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 28, 2008

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 29, 2008

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 10, 2011

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 8, 2011

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Valproic Acid-Albumin

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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