Vitamin D Supplementation for Adults With Neurofibromatosis Type 1 (NF1) (VitDBoneNF1)

A Phase II Trial on the Effect of Low-Dose Versus High-Dose Vitamin D Supplementation on Bone Mass in Adults With Neurofibromatosis Type 1 (NF1)

This clinical trial is conducted by one of 4 locations; University of British Columbia (Vancouver, CA), University of Utah (Salt Lake City, UT, USA), University of Cincinnati (Cincinnati, OH, USA), and University of Hamburg (Hamburg, Germany).

Adults with NF1 have a higher risk of osteopenia and osteoporosis, a condition of low bone density that can lead to fragile bones and bone breakage.

People with NF1 also have lower vitamin D levels than unaffected individuals. Vitamin D is important for normal bone health, but studies to improve bone health by vitamin D supplementation in people with NF1 have not been tried.

The purpose of this study is to treat adults with NF1 who have insufficient serum vitamin D levels with 2 different doses of vitamin D supplementation to determine if vitamin D supplementation ameliorates the usual loss of bone mineral density over 2 years.

Study Overview

• Status: Terminated
• Conditions: Neurofibromatosis Type 1 (NF1)
• Intervention / Treatment: Drug: Cholecalciferol

Detailed Description

Individuals with NF1 and vitamin D insufficiency will be supplemented with 2 different doses of cholecalciferol (vitamin D) to see if their loss of bone mineral density is lessened over time. It is important to study vitamins as carefully as one would study medications, even though vitamins are generally safer than medications. For this reason, a carefully controlled trial of two doses of vitamin D will be performed over a 2-year period. It will include controlled doses and safety checks for participants' health to be sure that the vitamin D supplementation is safe for people with NF1.

Two different doses of cholecalciferol, either 600 IU or 4,000 IU (IU means "International Units" a standard measure of the strength of the dose), will be used for supplementation. The trial is "double blind". This means that neither participant nor investigator team know which dose an individual participant might be randomized to receive until after the trial ends. In an emergency, however, the investigator can find out.

Participants will be randomized to one or the other dose, and each participant will be provided a bottle of liquid called "D-drops" with a dropper that automatically drops out a measured amount when the bottle is turned upside down.

Both doses of vitamin D, 600 IU and 4,000 IU, have been approved in the general population; however, it is possible that the bodies of people with NF1 handle vitamin D differently. Therefore, safety measures are assessed during this trial. Any new medical issues or concerns throughout the 2-year period will need to be recorded and assessed with the study team.

The primary measure of this study is bone mineral density obtained by bone densitometry (DXA) using low-dose xrays. Bone mineral density will be tested at the beginning and the end of the trial focusing on density of bones in the hip and spine. Secondary measures of this trial include questionnaires that measure quality of life and history of bone fractures.

When someone is insufficient in serum vitamin D and supplementation is recommended, it is also supplemented with calcium. Therefore, participants will be given a calcium supplement of 400 mg elemental calcium per day. A diary to keep daily track of vitamin D and calcium supplementation and documentation of fractures, should they occur, is provided.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T 1Z4
      • University of British Columbia
• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 23 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

All individuals with NF1 (neurofibromatosis type 1), based on NIH diagnostic criteria, who are between the ages of 25 and 40 years, may participate in this study. All participants will be enrolled in the study and then screened for serum 25(OH)D levels, and all individuals with levels between 9 and 29ng/ml (inclusive) are eligible for vitamin D supplementation -

Exclusion Criteria:

1. diagnosis of Paget's disease, hyperthyroidism, hyperparathyroidism, or other medical condition that affects bone health
2. they foresee that they will be unable to comply with the two-year study protocol
3. Pregnant, planning to conceive within the next two years, or is less than 6 months post-delivery or lactation.
4. vitamin D supplementation in the last 3 months equal to or greater than 600IU per day
5. oral or IV glucocorticoid use for over 3 months
6. bisphosphonate therapy for more than 3 months
7. calcitonin therapy for more than 3 months
8. calcium supplementation in last 3 months equal to or greater than 1000mg per day
9. malignant peripheral nerve sheath tumor (MPNST)
10. history of kidney stones in last 5 years
11. individuals with metal instrumentation in spine or hip that preclude accurate DXA interpretation.
12. inability to obtain blood samples on routine venipuncture
13. anti-epileptic medical therapy
14. anticoagulant medical therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: cholecalciferol 600 IU; cholecalciferol in Ddrops form at either 600 International units per day versus 4,000 IU per day	Drug: Cholecalciferol; DDrops(trademark) prepared two sets of bottles, one set has 300IU per metered dose and the other set has 2,000IU per metered dose. Participants are randomized to either 600 IU or 4,000 IU, and they take two measured drops orally, once a day. There is a dropper that automatically drops out a measured amount when the bottle is turned upside down.; Other Names: Vitamin D; D Drops; Dietary Supplement
Active Comparator: cholecalciferol 4,000 IU; Cholecalciferol at 4,000 IU per day in the form of liquid Ddrops	Drug: Cholecalciferol; DDrops(trademark) prepared two sets of bottles, one set has 300IU per metered dose and the other set has 2,000IU per metered dose. Participants are randomized to either 600 IU or 4,000 IU, and they take two measured drops orally, once a day. There is a dropper that automatically drops out a measured amount when the bottle is turned upside down.; Other Names: Vitamin D; D Drops; Dietary Supplement

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone mineral density	The primary outcome measure is a change in bone mineral density, which will be determined by bone densitometry at the beginning and at the end of the 2-year trial.	Change from Day 1 to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone Fractures	Secondary outcome measure of history of bone fractures.	change from Day 1 through 2 years
Quality of life questionnaires	Secondary outcome measures include quality of life	change from Day 1 through 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parathyroid hormone with calcium	Serum samples will be analyzed for intact parathyroid hormone with calcium.	change from day1 through year 2
25(OH) vitamin D	Serum samples will be analyzed for 25(OH) vitamin D	change from day1 through year 2

Collaborators and Investigators

• Sponsor: University of Utah
• Collaborators: University of British Columbia; Children's Hospital Medical Center, Cincinnati; U.S. Army Medical Research and Development Command; Universitätsklinikum Hamburg-Eppendorf
• Investigators: Principal Investigator: David H. Viskochil, MD, PhD, University of Utah

Publications and helpful links

General Publications

• Schnabel C, Jett K, Friedman JM, Frieling I, Kruse HP, Mautner V. Effect of vitamin D3 treatment on bone density in neurofibromatosis 1 patients: a retrospective clinical study. Joint Bone Spine. 2013 May;80(3):315-9. doi: 10.1016/j.jbspin.2012.07.010. Epub 2012 Sep 26.

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2017
• Primary Completion (Actual): January 1, 2022
• Study Completion (Actual): January 1, 2022

Study Registration Dates

• First Submitted: October 7, 2013
• First Submitted That Met QC Criteria: October 19, 2013
• First Posted (Estimate): October 24, 2013

Study Record Updates

• Last Update Posted (Actual): May 25, 2022
• Last Update Submitted That Met QC Criteria: May 17, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Vitamin D; Cholecalciferol; Bone density
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Genetic Diseases, Inborn; Neuromuscular Diseases; Neurodegenerative Diseases; Neoplasms, Nerve Tissue; Peripheral Nervous System Diseases; Nervous System Neoplasms; Heredodegenerative Disorders, Nervous System; Neoplastic Syndromes, Hereditary; Nerve Sheath Neoplasms; Neurocutaneous Syndromes; Peripheral Nervous System Neoplasms; Neurofibromatoses; Neurofibromatosis 1; Neurofibroma; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: DoD A-17236; W18XWH-12-1-0487 (Other Grant/Funding Number: Department of Defense NF Research Program)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Publication of all study data will be written

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No