Trial of Lithium Carbonate for Treatment of Osteoporosis-pseudoglioma Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01108068
Recruitment Status : Completed
First Posted : April 21, 2010
Last Update Posted : December 2, 2015
Information provided by (Responsible Party):
Elizabeth Streeten, University of Maryland

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.

Condition or disease Intervention/treatment Phase
Osteoporosis Pseudoglioma Drug: Lithium Not Applicable

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Arm Intervention/treatment
Experimental: Lithium
patients with OPPG will be treated with lithium for 6 months
Drug: Lithium
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.

Primary Outcome Measures :
  1. 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

Secondary Outcome Measures :
  1. 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.

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Ages Eligible for Study:   4 Years to 64 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

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 identifier (NCT number): NCT01108068

United States, Pennsylvania
University of Maryland Amish Research Clinic
Lancaster, Pennsylvania, United States, 17601
Sponsors and Collaborators
University of Maryland
Principal Investigator: Elizabeth A Streeten, MD University of Maryland

Responsible Party: Elizabeth Streeten, Associate Professor of Medicine, University of Maryland Identifier: NCT01108068     History of Changes
Other Study ID Numbers: HP-40536
First Posted: April 21, 2010    Key Record Dates
Last Update Posted: December 2, 2015
Last Verified: December 2015

Keywords provided by Elizabeth Streeten, University of Maryland:
Osteoporosis-pseudoglioma syndrome, OPPG, LRP5 mutation

Additional relevant MeSH terms:
Spasms, Infantile
Genetic Diseases, X-Linked
Osteogenesis Imperfecta
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Metabolic Diseases
Vision Disorders
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Eye Diseases
Signs and Symptoms
Epilepsy, Generalized
Brain Diseases
Central Nervous System Diseases
Genetic Diseases, Inborn
Bone Diseases, Developmental
Collagen Diseases
Connective Tissue Diseases
Lithium Carbonate
Antidepressive Agents
Psychotropic Drugs
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimanic Agents