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
|Official Title:||Trial of Lithium Carbonate for Treatment of Osteoporosis Pseudoglioma Syndrome|
- pQCT of forearm and lower leg [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: Yes ]pQCT will be done at baseline and after 6 months of lithium to assess changes in bone quality
- Fracture [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]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.
|Study Start Date:||July 2010|
|Study Completion Date:||July 2014|
|Primary Completion Date:||July 2014 (Final data collection date for primary outcome measure)|
patients with OPPG will be treated with lithium for 6 months
lithium will be given for 6 months to patients with OPPG, starting at a low dose of 2.5 mg/kg daily, gradually increasing until a lithium blood level of 0.3-0.6 ng/dl is achieved.
Other Name: lithium carbonate or lithium citrate will be used
No Intervention: Unaffected controls
Family members of patients with OPPG will have DXA and pQCT to compare to OPPG patients. These unaffected participants will not receive lithium.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01108068
|United States, Pennsylvania|
|University of Maryland Amish Research Clinic|
|Lancaster, Pennsylvania, United States, 17601|
|Principal Investigator:||Elizabeth A Streeten, MD||University of Maryland|