Oxidative Stress Markers In Inherited Homocystinuria And The Impact Of Taurine

NCT01192828 | Completed Phase 1 Results

• 2 other identifiers: 08-1376FDR003907
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 4

Brief Summary

Cystathionine beta-synthase deficiency is an inherited disease that results in elevation of a substance called homocysteine (Hcy) in blood and urine. Individuals with this disorder have a very high risk for developing blood clots and are at risk for developing eye and bone abnormalities. Current treatments are generally difficult to follow and can fail. Development of additional therapies has been limited by lack of understanding of how the disease works. The purpose of this study is to see if oxidative stress and inflammation are involved in the disease process and if short-term supplementation with taurine is an effective treatment. Funding source: FDA.

Conditions

Homocystinuria

Keywords

cystathionine beta-synthase (CBS)

Outcome Measures

Primary Outcomes (2)

• Difference in Thiobarbituric Acid Reactive Substances (TBARS) in Individuals With Cystathionine Beta Synthase Deficient Homocystinuria (CBSDH) Pre and Post Taurine Treatment.

  TBARS were measured in plasma via colorimetric absorbance. TBARS are a marker of oxidative stress. They are formed as a by-product of lipid (fat) oxidation. TBARS predominantly reflect the level of malondialdehyde (MDA) a substance that is formed from the breakdown of polyunsaturated fatty acids.

  Baseline and after 4 days of therapy.

• Difference in Tumor Necrosis Factor Alpha (TNF-alpha) in Individuals With CBSDH Pre and Post Taurine Treatment.

  TNF-alpha was measured in plasma via Luminex high sensitivity assay. TNF-alpha is a signaling protein, or cytokine that promotes an inflammatory response.

  Baseline and after 4 days of treatment.

Secondary Outcomes (4)

• Difference in Endothelial Function (Blood Vessel Function) in Individuals With CBSDH Pre and Post Taurine Treatment

  Baseline and after 4.5 days of taurine treatment

• Difference in Endothelial Function (Blood Vessel Function) in Individuals With CBSDH and Homocysteine Levels Greater Than 125 Micromole/L Pre and Post Taurine Treatment.

  Baseline and after 4.5 days of therapy.

• Difference in Endothelial Function (Blood Vessel Function) in Individuals With CBSDH and Pre Taurine Exposure FMD Values Less Than 10 mm Pre and Post Taurine Treatment.

  Baseline and after 4.5 days of therapy.

• Percent of Individuals With Decreased Bone Mineral Density.

  Baseline

Other Outcomes (6)

• Thiobarbituric Acid Reactive Substances (TBARS) in Individuals With CBSDH Compare to Homocysteine Level.

  Baseline

• Determination of Baseline Taurine Level, Peak Taurine Level on Day One, Trough Level on Day One and Trough Level on Day Four of Taurine Treatment.

  Taurine levels were obtained prior to taurine adminstration and at , t=0.5, t=1, t=2, t=3, t=4, t=6, t=8, t=12 and 96 hours.

• Difference in Triglycerides in Individuals With CBSDH Receiving Both Low Dose and Target Dose Taurine Pre and Post Taurine Treatment (Safety Assessment)

  Baseline and after 4 days of treatment.

Study Arms (1)

Taurine

EXPERIMENTAL

Treatment with Taurine

Drug: taurine

Interventions

taurine DRUG

Take Taurine for 4 1/2 days, two doses per day

Also known as: Not Applicable. No other names.

Taurine

Eligibility Criteria

• Age: 8 Years - 49 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• A confirmed biochemical, molecular, or enzymatic diagnosis of classic homocystinuria due to cystathionine beta-synthase deficiency (OMIM 236200)
• And not fully responsive to therapy (eg, total homocysteine (tHcy) levels above 50 µmol/L on therapy including on B6 therapy)
• Be over 8 years old and less than 50 years. The first four patients will be adults (age 18-50 years)
• Be able and willing to provide informed consent

You may not qualify if:

• Pregnancy: Females who are pregnant or lactating will be excluded from the study as the influence of pregnancy on the markers is not known nor is the safety of taurine supplementation in pregnancy.
• Continued antioxidant intake:
• Individuals currently taking taurine, over the counter energy drinks containing taurine or other high dose antioxidants and unwilling to discontinue this for the study period (including a 2 week wash out period) will be excluded as such intake will likely impact laboratory results.
• Individuals taking Vitamin C as a prescribed treatment for their homocystinuria will be excluded as the antioxidant therapy may impact antioxidant and inflammation markers. (As Vitamin C is not standard of care for this disease we anticipate this to have minimal impact on recruitment.)
• Individuals currently taking platelet aggregation inhibitors such as salicylate on a self prescribed basis and unwilling to discontinue this for the study period (including a washout period of at least two weeks prior to the study) will be excluded as salicylate intake will impact platelet study results. Individuals taking salicylate (or other platelet aggregation inhibitors) prescribed as a therapy for their homocystinuria or other health issues will not be asked to stop the medication. They will participate in the study, but will be excluded only from the platelet studies.
• Medication interactions: Individuals unable or unwilling to abstain from use of cyclic guanosine monophosphate (cGMP) phosphodiesterase 5 inhibitors (such as Viagra) during the study period will be excluded from the nitroglycerin-induced flow-mediated dilatation studies in accordance with known labeling contraindications.
• Inflammatory status:
• Individuals who have a significant chronic illness that has a marked inflammatory component will be excluded from the study as the illness will impact inflammatory markers.
• Patients with an acute illness, which may impact inflammatory biomarkers, will be postponed for study entry until the acute illness is resolved. Entry into the study at a later day will be offered.
• Recent cardiovascular event. Cardiovascular events (stroke, myocardial infarct, deep vein thrombosis, pulmonary embolus, thrombosis, or uncontrolled hypertension) may interfere with platelet function studies and with various mediators during the first months after the event. Patients who had such an event within the last 6 months will be excluded.
• Hypertriglyceridemia. Individuals with a triglyceride level above 300 mg/dl will be excluded from the study.
• Informed consent: Individuals who are unwilling or unable to consent, or in the case of minors who are unwilling or unable to assent will be excluded due to lack of ability to ensure informed consent.
• Study compliance and integrity: Individual who anticipate an inability to comply with study procedures and requirements will be excluded.

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (4)

Childrens Hospital Colorado

Aurora, Colorado, 80045, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Duke University

Durham, North Carolina, 27708, United States

Location

Childrens Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Homocystinuria

Interventions

Taurine

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hyperhomocysteinemia; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Dr. Johan Van Hove, Primary Investigator
• Organization: University of Colorado Denver

johan.vanhove@childrenscolorado.org

303-724-2338

Study Officials

• Johan VanHove, MD PhD MBA

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2010
• First Posted: September 1, 2010
• Study Start: January 1, 2010
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: July 9, 2018
• Results First Posted: July 9, 2018

Record last verified: 2018-06

Locations

US (4)