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

NCT03582384 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: IRB-P00026926
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (1)

• Vitamin E Level

  Primary outcomes measured will include whether the vitamin E level increased to \> 5 mg/L

  1 Year

Study Arms (1)

Treatment

EXPERIMENTAL

Drug: Tocofersolan

Interventions

Tocofersolan 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.

Treatment

Eligibility Criteria

• Age: 30 Days - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• \. 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.

You may not qualify if:

• Pregnancy
• Use of warfarin or any related vitamin K antagonist.
• Enrollment in any other clinical trial involving an investigational agent (unless approved by the principal investigators of the other trial)
• The parent or guardian or child unwilling to provide consent or assent

Sponsors & Collaborators

• Boston Children's Hospital: lead

Related Publications (8)

• 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.

  PMID: 19823814 BACKGROUND

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

  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.

  PMID: 27429361 BACKGROUND

• 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.

  PMID: 27429423 BACKGROUND

• 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.

  PMID: 23978355 BACKGROUND

• 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.

  PMID: 12537931 BACKGROUND

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

  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.

  PMID: 21324480 RESULT

MeSH Terms

Conditions

Short Bowel Syndrome; Vitamin E Deficiency

Interventions

tocophersolan

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Research Specialist

Study Record Dates

• First Submitted: June 26, 2018
• First Posted: July 11, 2018
• Study Start: December 1, 2020
• Primary Completion: January 1, 2022
• Study Completion: January 1, 2023
• Last Updated: May 13, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share