Carnitine Transporter DeficiencyNCT00187733
Influence of OCTN2 Variants on Carnitine Status and Plasma Triglycerides
An observational study of Carnitine Transporter Deficiency, run by University of California, San Francisco at 1 site in United States.
Trial summary
The current study is part of a large multi-investigator grant to look at the pharmacogenetics of a number of membrane transporters. Previously, the investigators have recruited a cohort of healthy volunteers (Studies of Pharmacogenetics in Ethnically-Diverse Populations, or SOPHIE) and have resequenced the coding… Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Carnitine Transporter Deficiency
- What is being tested?
- Fasting blood and urine collection
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2005to Feb 2008
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: Healthy individuals per screening laboratory results and health questionnaire
Who may be able to join
- Previous participation in the "SOPHIE" study
- Between the ages of 18 and 40 years old
- Have a pre-selected genotype for OCTN1 and OCTN2
- Have been selected as healthy by medical history questionnaire and screening blood work (complete blood count [CBC], comprehensive metabolic panel).
Who cannot join
- Pregnant at the time of the study
- Have a new history indicating they are no longer healthy
- Taking a medication that could confound study results
- Individuals with anemia (hemoglobin < 12 g/dL), an elevation in liver enzymes to higher than double the respective normal value, or elevated creatinine concentrations (males ≥ 1.5 mg/dL, females ≥ 1.4 mg/dL).
- Do not consent to participate in the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
San Francisco General Hospital
San Francisco, California, 94143
About this study
The current study is part of a large multi-investigator grant to look at the pharmacogenetics of a number of membrane transporters. Previously, the investigators have recruited a cohort of healthy volunteers (Studies of Pharmacogenetics in Ethnically-Diverse Populations, or SOPHIE) and have resequenced the coding region of a number of membrane transporter genes to identify genetic polymorphisms in these genes. Subjects in this cohort have agreed to be called back for recruitment in further studies based on their own genetic sequence, allowing the investigators the possibility to prospectively study the influence of genetic polymorphisms on particular phenotypes (i.e., genotype-to-phenotype studies). The investigators plan to take a genotype-to-phenotype approach to study the influence of specific polymorphisms in the novel organic cation transporter 2 (OCTN2) gene on carnitine and lipid metabolism in healthy subjects.
Read the detailed description
Although OCTN2 is fairly well studied in its relationship with SCD, little is known about the carrier frequency of disease-causing alleles of OCTN2, or of more common functional polymorphisms in this gene. To address these issues, we screened for genetic variants in the OCTN2 coding region by direct sequencing of the exons and flanking intronic region of OCTN2 in a large sample (n = 276) of ethnically diverse subjects. In addition, we established lymphoblastoid cell lines from subjects homozygous for either allele of the previously identified promoter region variant, -207G>C. We found eight amino acid sequence variants of OCTN2, of which three (Phe17Leu, Leu144Phe, and Pro549Ser) were polymorphic in at least one ethnic group. When assayed for functional activity by expression in human embryonic kidney 293 cells, using as probes both the endogenous substrate (l-carnitine) and the organic cation tetraethylammonium, three variants showed functional differences from the reference OCTN2 (Phe17Leu, Tyr449Asp, Val481Phe; p < 0.05). Further studies of the Phe17Leu polymorphism showed a reduced V(max) for l-carnitine transport to approximately 50% of the reference OCTN2. Confocal microscopy studies using an OCTN2-GFP fusion protein showed that Phe17Leu had distinct subcellular localization from the reference OCTN2, with diffuse cytoplasmic retention of Phe17Leu, in contrast to reference OCTN2, which localized specifically to the plasma membrane. Lymphoblasts from subjects homozygous for the -207G allele showed increased l-carnitine transport compared with the -207C/C homozygotes (p < 0.05). This study suggests that although loss-of-function mutations in OCTN2 are likely to be rare, common variants of OCTN2 found in healthy populations may contribute to variation in the disposition of carnitine and some clinically used drugs.
- Conditions
- Carnitine Transporter Deficiency
- Being tested
- Fasting blood and urine collection
- Keywords
- L-carnitine
- Medical subject headings
- Systemic carnitine deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fasting blood and urine collectionOther
Not applicable no drugs dispensed
| Study group | Role | What they receive |
|---|---|---|
| Fasting | Other: Fasting blood and urine collection Receives: Other: Fasting blood and urine collection |
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2005 (estimated)
- Study startJan 2005
- Primary completionFeb 2008
- Study completionFeb 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Carnitine Transporter DeficiencyStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kathleen Giacomini, PhD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00187733
- Sponsor's protocol ID
- 1005
- Status last verified
- Sep 2012
- First submitted
- 14 Sep 2005
- Last updated
- 13 Sep 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Urban TJ, Gallagher RC, Brown C, Castro RA, Lagpacan LL, Brett CM, Taylor TR, Carlson EJ, Ferrin TE, Burchard EG, Packman S, Giacomini KM. Functional genetic diversity in the high-affinity carnitine transporter OCTN2 (SLC22A5). Mol Pharmacol. 2006 Nov;70(5):1602-11. doi: 10.1124/mol.106.028126. Epub 2006 Aug 24.
PubMed 16931768
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influence of OCTN2 Variants on Carnitine Status and Plasma Triglycerides
- ClinicalTrials.gov ID
- NCT00187733
- Acronym / sponsor ID
- 1005
- Conditions
- Carnitine Transporter Deficiency
- Keywords
- L-carnitine
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- Jan 2005
- Primary completion
- Feb 2008 (actual)
- Study completion
- Feb 2008 (actual)
- First posted
- 16 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The current study is part of a large multi-investigator grant to look at the pharmacogenetics of a number of membrane transporters. Previously, the investigators have recruited a cohort of healthy volunteers (Studies of Pharmacogenetics in Ethnically-Diverse Populations, or SOPHIE) and have resequenced the coding region of a number of membrane transporter genes to identify genetic polymorphisms in these genes. Subjects in this cohort have agreed to be called back for recruitment in further studies based on their own genetic sequence, allowing the investigators the possibility to prospectively study the influence of genetic polymorphisms on particular phenotypes (i.e., genotype-to-phenotype studies). The investigators plan to take a genotype-to-phenotype approach to study the influence of specific polymorphisms in the novel organic cation transporter 2 (OCTN2) gene on carnitine and lipid metabolism in healthy subjects.
Detailed description
Although OCTN2 is fairly well studied in its relationship with SCD, little is known about the carrier frequency of disease-causing alleles of OCTN2, or of more common functional polymorphisms in this gene. To address these issues, we screened for genetic variants in the OCTN2 coding region by direct sequencing of the exons and flanking intronic region of OCTN2 in a large sample (n = 276) of ethnically diverse subjects. In addition, we established lymphoblastoid cell lines from subjects homozygous for either allele of the previously identified promoter region variant, -207G>C. We found eight amino acid sequence variants of OCTN2, of which three (Phe17Leu, Leu144Phe, and Pro549Ser) were polymorphic in at least one ethnic group. When assayed for functional activity by expression in human embryonic kidney 293 cells, using as probes both the endogenous substrate (l-carnitine) and the organic cation tetraethylammonium, three variants showed functional differences from the reference OCTN2 (Phe17Leu, Tyr449Asp, Val481Phe; p < 0.05). Further studies of the Phe17Leu polymorphism showed a reduced V(max) for l-carnitine transport to approximately 50% of the reference OCTN2. Confocal microscopy studies using an OCTN2-GFP fusion protein showed that Phe17Leu had distinct subcellular localization from the reference OCTN2, with diffuse cytoplasmic retention of Phe17Leu, in contrast to reference OCTN2, which localized specifically to the plasma membrane. Lymphoblasts from subjects homozygous for the -207G allele showed increased l-carnitine transport compared with the -207C/C homozygotes (p < 0.05). This study suggests that although loss-of-function mutations in OCTN2 are likely to be rare, common variants of OCTN2 found in healthy populations may contribute to variation in the disposition of carnitine and some clinically used drugs.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Fasting | – | Other: Fasting blood and urine collectionOther: Fasting blood and urine collection |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Healthy individuals per screening laboratory results and health questionnaire
Key inclusion criteria (4 listed)
- Previous participation in the "SOPHIE" study
- Between the ages of 18 and 40 years old
- Have a pre-selected genotype for OCTN1 and OCTN2
- Have been selected as healthy by medical history questionnaire and screening blood work (complete blood count [CBC], comprehensive metabolic panel).
Key exclusion criteria (5 listed)
- Pregnant at the time of the study
- Have a new history indicating they are no longer healthy
- Taking a medication that could confound study results
- Individuals with anemia (hemoglobin < 12 g/dL), an elevation in liver enzymes to higher than double the respective normal value, or elevated creatinine concentrations (males ≥ 1.5 mg/dL, females ≥ 1.4 mg/dL).
- Do not consent to participate in the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fasting blood and urine collectionNot applicable no drugs dispensed | Other | Fasting |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2012.
- Results publication: PubMed 16931768Urban TJ, Gallagher RC, Brown C, Castro RA, Lagpacan LL, Brett CM, Taylor TR, Carlson EJ, Ferrin TE, Burchard EG, Packman S, Giacomini KM. Functional genetic diversity in the high-affinity carnitine transporter OCTN2 (SLC22A5). Mol Pharmacol. 2006 Nov;70(5):1602-11. doi: 10.1124/mol.106.028126. Epub 2006 Aug 24.
Related trials for Carnitine Transporter Deficiency
Active, not recruitingObservational study
Early Check: Expanded Screening in Newborns
Spinal Muscular Atrophy, Fragile X Syndrome
RecruitingEarly Phase 1
Oral Carnitine in Heart Failure Patients
Heart Failure, Carnitine Deficiency
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kathleen Giacomini, PhD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Carnitine Transporter Deficiency, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Sep 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00187733, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2012.