Clinical Trial: Trial of Lithium Carbonate for Treatment of Osteoporosis-pseudoglioma Syndrome

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Trial of Lithium Carbonate for Treatment of Osteoporosis Pseudoglioma Syndrome

Brief 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.

Detailed Summary:

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 l
Sponsor: University of Maryland

Current Primary Outcome: pQCT of forearm and lower leg [ Time Frame: Baseline and 6 months ]

pQCT will be done at baseline and after 6 months of lithium to assess changes in bone quality


Original Primary Outcome: Same as current

Current Secondary Outcome: Fracture [ Time Frame: Baseline and 12 months ]

Fractures will be monitored from baseline to 12 months after starting lithium and will be compared to fractures occurring during the 12 months prior to starting lithium.


Original Secondary Outcome: Same as current

Information By: University of Maryland

Dates:
Date Received: April 20, 2010
Date Started: July 2010
Date Completion:
Last Updated: December 1, 2015
Last Verified: December 2015