Trial of Lithium Carbonate for Treatment of Osteoporosis-pseudoglioma Syndrome
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|ClinicalTrials.gov Identifier: NCT01108068|
Recruitment Status : Completed
First Posted : April 21, 2010
Results First Posted : April 27, 2018
Last Update Posted : November 4, 2019
|Condition or disease||Intervention/treatment||Phase|
|Osteoporosis Pseudoglioma||Drug: Lithium||Not Applicable|
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 recruited 10 patients with OPPG and treated those who agreed (n=5) 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 was obtained to use lithium in this study.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||26 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Trial of Lithium Carbonate for Treatment of Osteoporosis Pseudoglioma Syndrome|
|Study Start Date :||July 2010|
|Actual Primary Completion Date :||July 2014|
|Actual Study Completion Date :||July 2014|
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.
- pQCT of Lower Leg [ Time Frame: Baseline ]pQCT will be done at baseline for all OPPG participants and unaffecteds. The Z-score indicates the number of standard deviations away from the mean of age matched controls. A Z-score of 0 is equal to the mean, with negative numbers indicating values lower than the mean and positive values higher. A positive change in Z-score indicates a favorable outcome.
- pQCT Z-score in OPPG Participants at Baseline and 6 Months After Lithium [ Time Frame: baseline, 6 months ]The Z-score indicates the number of standard deviations away from the mean of age matched controls. A Z-score of 0 is equal to the mean, with negative numbers indicating values lower than the mean and positive values higher. A positive change in Z-score indicates a favorable outcome.Z-score of pQCT variable was noted for the in two OPPG participants who received lithium and were also able to get pQCT scans. The "n" of 2 was too small to do statistical analyses. Of the 5 OPPG who were on lithium, 2 were too small for the machine (eventhough over age 4) and 1 had rods in his legs and couldn't have pQCT
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01108068
|United States, Pennsylvania|
|University of Maryland Amish Research Clinic|
|Lancaster, Pennsylvania, United States, 17601|
|Principal Investigator:||Elizabeth A Streeten, MD||University of Maryland, College Park|