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

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.

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