Trial of Lithium Carbonate for Treatment of Osteoporosis-pseudoglioma Syndrome
Information source: University of Maryland
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Osteoporosis Pseudoglioma
Intervention: Lithium (Drug)
Phase: N/A
Status: Active, not recruiting
Sponsored by: University of Maryland Official(s) and/or principal investigator(s): Elizabeth A Streeten, MD, Principal Investigator, Affiliation: University of Maryland
Summary
This is a pilot study of up to 10 patients with Osteoporosis-pseudoglioma syndrome (OPPG)
from the Old Order Mennonite community, who will be given lithium for 6 months and have dual
energy xray absorptiometry (DXA), peripheral quantitative computerized tomography (pQCT) and
lab assessment at baseline and 6 months. Studies in the mouse model of OPPG showed that
lithium normalized their bone strength. Controls (n=20) will be recruited from the Old Order
Mennonite community, to minimize the effects of environmental and lifestyle factors. The
controls will not be given lithium. The age range of participants will be 4-64 years.
Clinical Details
Official title: Trial of Lithium Carbonate for Treatment of Osteoporosis Pseudoglioma Syndrome
Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: pQCT of forearm and lower leg
Secondary outcome: Fracture
Detailed description:
Osteoporosis-pseudoglioma (OPPG) syndrome is a very rare genetic disorder (approximately 50
cases have been reported worldwide) due to mutations in the LRP5 gene, causing blindness
from birth and fragile bones (osteoporosis)in early childhood. The bony fragility can lead
to recurrent fractures of major bones such as the hip (femur) and spine, leaving some
children in wheelchairs.
Treatment to strengthen the bones in OPPG has primarily been with osteoporosis medications
used in other fragile bone disorders of childhood and in adults, namely the bisphosphonates
(eg. pamidronate, alendronate). These drugs have helped the bone strength in OPPG somewhat
but have not prevented all fractures. We have observed fractures of the hip in 3 children
with OPPG who we have treated, in spite of their attaining normal bone density (determined
by DXA, dual xray absorptiometry) with bisphosphonates. Therefore, new treatments for OPPG
are greatly needed and new methods besides DXA are needed to monitor bone strength on
treatment.
A mouse model of OPPG has been created. In the mouse model of OPPG, lithium dramatically
improved their bones, returning them to normal strength and preventing fractures. Lithium,
which is used for people with psychiatric disease, is known to lead to higher bone strength
and reduced fractures in people who are on it for psychiatric disease. Lithium has been used
safely and is approved for children 12 and above. The theory is that lithium will improve
bone strength in OPPG in humans, as it has in the mouse, by stimulating bone production
bypassing the genetic defect in OPPG.
In this study, we plan to treat up to 10 patients with OPPG with lithium for 6 months,
monitoring the response of the bones by both DXA and pQCT (peripheral quantitative computed
tomography), the latter which gives information about bone quality. An IND has been obtained
to use lithium in this study.
Eligibility
Minimum age: 4 Years.
Maximum age: 64 Years.
Gender(s): Both.
Criteria:
Eligibility Criteria
Inclusion Criteria
- Age 4 years or greater
- Diagnosed with osteoporosis pseudoglioma syndrome (OPPG) or a first degree relative
of someone with OPPG. For diagnosis of OPPG, one of the following is required: (1)
congenital blindness in a child born into a family with known OPPG where at least one
affected family member has had an LRP5 mutation demonstrated or (2) a child with no
known family members with OPPG who has congenital blindness, DXA Z-score < - 2. 0 and
mutation in LRP5 documented
- No contraindications to lithium carbonate
- For women of child bearing age, willing to undergo urine pregnancy test
Exclusion Criteria
- Age under 4 years
- Not diagnosed with osteoporosis pseudoglioma (OPPG) syndrome or a first degree
relative of someone with OPPG, or a member of the Old Order Mennonite community
- Pregnant
- For women of childbearing age, not willing to undergo urine pregnancy test
- Contraindication to Lithium (serum creatinine > 1. 3, known cardiovascular disease
[history of myocardial infarction, heart failure], currently on diuretic or ACE
inhibitor)
- Glomerular filtration rate below 80 cc/min
Locations and Contacts
University of Maryland Amish Research Clinic, Lancaster, Pennsylvania 17601, United States
Additional Information
Related publications: Streeten EA, McBride D, Puffenberger E, Hoffman ME, Pollin TI, Donnelly P, Sack P, Morton H. Osteoporosis-pseudoglioma syndrome: description of 9 new cases and beneficial response to bisphosphonates. Bone. 2008 Sep;43(3):584-90. doi: 10.1016/j.bone.2008.04.020. Epub 2008 May 7. Clément-Lacroix P, Ai M, Morvan F, Roman-Roman S, Vayssière B, Belleville C, Estrera K, Warman ML, Baron R, Rawadi G. Lrp5-independent activation of Wnt signaling by lithium chloride increases bone formation and bone mass in mice. Proc Natl Acad Sci U S A. 2005 Nov 29;102(48):17406-11. Epub 2005 Nov 17.
Starting date: July 2010
Last updated: December 9, 2013
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