Use of Tocofersolan (Vedrop®) to Prevent or Treat Refractive Vitamin E Deficiency in Infants and Children

NCT ID: NCT03582384

Last Updated: 2020-05-13

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-31
• Study Completion Date: 2023-01-31

Brief Summary

Patients with short bowel syndrome or other forms of intestinal failure/fat malabsorption are unable to tolerate adequate oral or enteral feedings. They require that nutrition be given as enteral nutrition that is delivered by feeding tube. Often these children take supplements such as vitamins to help improve their nutritional status but, due to their condition, they have difficulty absorbing the supplement sufficiently and most of it is lost in the stool. The drug that will be studied, Tocofersolan (Vedrop®) is a form of vitamin E, a type of the fat soluble vitamin needed in the human diet. It has been formulated in such a way that it may be more easily absorbed by patients with this condition. The main purpose of the study is to learn about the safety and tolerability of this form of vitamin E. Before receiving the study drug, the severity of the child's vitamin E deficiency will be determined by a blood sample, followed by giving them a daily dose of tocofersolan (Vedrop®) either orally or through their feeding tube. After a 4 weeks of therapy, a second blood sample will be checked and the child will continue either same dose of tocoferssolan or it will be adjusted in response to the blood levels. If the study drug works as it is designed to do, there should be an increase in the concentration of the vitamin E in the child's blood, suggesting that the drug was absorbed. At each visit, a sample of blood will be obtained to assess the child's vitamin E status and general health.

Patients will remain on tocofersolan for approximately one year or as long as the study remains open. Based on the European pediatric experience, patients should be expected be on tocofersolan a minimum of 3 months, ideally 6 months to see optimal clinical response.

Conditions

Short Bowel Syndrome; Vitamin E Deficiency

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

Group Type: EXPERIMENTAL

Tocofersolan

Intervention Type: DRUG

After baseline labs are obtained, therapy with tocofersolan will be initiated at an initial dose of 17 mg/kg of d-alpha-tocopherol in the form of tocofersolan (0.34 ml/kg/day) and titrated based on blood levels.

Interventions

Tocofersolan

After baseline labs are obtained, therapy with tocofersolan will be initiated at an initial dose of 17 mg/kg of d-alpha-tocopherol in the form of tocofersolan (0.34 ml/kg/day) and titrated based on blood levels.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patients with intestinal failure or fat malabsorption who have refractory vitamin E deficiency (defined as vitamin E level < 5 mg/L) despite receiving vitamin E supplementation with currently available enteral vitamin E products for at least 6 months or requiring the provision of vitamin parenterally as part of a multivitamin infusion.

Exclusion Criteria

1. Pregnancy

2. Use of warfarin or any related vitamin K antagonist.

3. Enrollment in any other clinical trial involving an investigational agent (unless approved by the principal investigators of the other trial)

4. The parent or guardian or child unwilling to provide consent or assent

• Minimum Eligible Age: 30 Days
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boston Children's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Daniel Elman

Clinical Research Specialist

Responsibility Role: PRINCIPAL_INVESTIGATOR

References

Westergren T, Kalikstad B. Dosage and formulation issues: oral vitamin E therapy in children. Eur J Clin Pharmacol. 2010 Feb;66(2):109-18. doi: 10.1007/s00228-009-0729-1. Epub 2009 Oct 13.

Reference Type: BACKGROUND

PMID: 19823814 (View on PubMed)

European Medicines Agency Evaluation of Medicines for Human Use, CHMP Assessment Report for Vedrop, London, 29 May 2009 Doc.Ref.: EMEA/485798/2009.

Reference Type: BACKGROUND

Sokol RJ. A New Old Treatment for Vitamin E Deficiency in Cholestasis. J Pediatr Gastroenterol Nutr. 2016 Dec;63(6):577-578. doi: 10.1097/MPG.0000000000001330. No abstract available.

Reference Type: BACKGROUND

PMID: 27429361 (View on PubMed)

Thebaut A, Nemeth A, Le Mouhaer J, Scheenstra R, Baumann U, Koot B, Gottrand F, Houwen R, Monard L, de Micheaux SL, Habes D, Jacquemin E. Oral Tocofersolan Corrects or Prevents Vitamin E Deficiency in Children With Chronic Cholestasis. J Pediatr Gastroenterol Nutr. 2016 Dec;63(6):610-615. doi: 10.1097/MPG.0000000000001331.

Reference Type: BACKGROUND

PMID: 27429423 (View on PubMed)

Ubesie AC, Kocoshis SA, Mezoff AG, Henderson CJ, Helmrath MA, Cole CR. Multiple micronutrient deficiencies among patients with intestinal failure during and after transition to enteral nutrition. J Pediatr. 2013 Dec;163(6):1692-6. doi: 10.1016/j.jpeds.2013.07.015. Epub 2013 Aug 24.

Reference Type: BACKGROUND

PMID: 23978355 (View on PubMed)

Zondlo Fiume M. Final report on the safety assessment of Tocopherol, Tocopheryl Acetate, Tocopheryl Linoleate, Tocopheryl Linoleate/Oleate, Tocopheryl Nicotinate, Tocopheryl Succinate, Dioleyl Tocopheryl Methylsilanol, Potassium Ascorbyl Tocopheryl Phosphate, and Tocophersolan. Int J Toxicol. 2002;21 Suppl 3:51-116. doi: 10.1080/10915810290169819. No abstract available.

Reference Type: BACKGROUND

PMID: 12537931 (View on PubMed)

Ash, M. (2004). Handbook of green chemicals (2nd ed.). Endicott, N.Y.: Synapse Information Resources.

Reference Type: BACKGROUND

Yang CF, Duro D, Zurakowski D, Lee M, Jaksic T, Duggan C. High prevalence of multiple micronutrient deficiencies in children with intestinal failure: a longitudinal study. J Pediatr. 2011 Jul;159(1):39-44.e1. doi: 10.1016/j.jpeds.2010.12.049. Epub 2011 Feb 16.

Reference Type: RESULT

PMID: 21324480 (View on PubMed)

Other Identifiers

IRB-P00026926

Identifier Type: -

Identifier Source: org_study_id