Trial of Lithium Carbonate for Treatment of Osteoporosis-pseudoglioma Syndrome

NCT01108068 | Completed Results DMC

• 1 other identifier: HP-00040536
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

This was a pilot study of 10 patients with Osteoporosis-pseudoglioma syndrome (OPPG) from the Old Order Mennonite community and 16 controls, who did not have OPPG. Five of the 10 OPPG patient elected to participate in the Lithium trial and 5 participated only in baseline data (labs, pQCT). The 5 with OPPG who were given lithium for 6 months had both 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=16) were recruited from the Old Order Mennonite community, to minimize the effects of environmental and lifestyle factors. The controls were not be given lithium. The age range of participants was 4-64 years.

Conditions

Osteoporosis Pseudoglioma

Keywords

Osteoporosis-pseudoglioma syndrome, OPPG, LRP5 mutation

Outcome Measures

Primary Outcomes (1)

• pQCT of Lower Leg

  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.

  Baseline

Secondary Outcomes (1)

• pQCT Z-score in OPPG Participants at Baseline and 6 Months After Lithium

  baseline, 6 months

Study Arms (2)

Lithium

EXPERIMENTAL

patients with OPPG will be treated with lithium for 6 months

Drug: Lithium

Unaffected controls

NO INTERVENTION

Family members of patients with OPPG will have DXA and pQCT to compare to OPPG patients. These unaffected participants will not receive lithium.

Interventions

Lithium DRUG

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.

Also known as: lithium carbonate or lithium citrate will be used

Lithium

Eligibility Criteria

• Age: 4 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (1)

University of Maryland Amish Research Clinic

Lancaster, Pennsylvania, 17601, United States

Location

Related Publications (3)

• 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.

  PMID: 18602879 BACKGROUND

• Clement-Lacroix P, Ai M, Morvan F, Roman-Roman S, Vayssiere 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. doi: 10.1073/pnas.0505259102. Epub 2005 Nov 17.

  PMID: 16293698 BACKGROUND

• Streeten EA, Ramirez S, Eliades M, Jaimungal S, Chandrasekaran S, Kathleen R, Holmes Morton D, Puffenberger EG, Herskovitz R, Leonard MB. Fractures on bisphosphonates in osteoporosis pseudoglioma syndrome (OPPG): pQCT shows poor bone density and structure. Bone. 2015 Aug;77:17-23. doi: 10.1016/j.bone.2015.04.007. Epub 2015 Apr 16.

  PMID: 25892485 BACKGROUND

MeSH Terms

Conditions

Exudative Vitreoretinopathy 4; Osteoporosis-pseudoglioma syndrome

Interventions

Lithium; Lithium Carbonate

Intervention Hierarchy (Ancestors)

Metals, Alkali; Elements; Inorganic Chemicals; Metals, Light; Metals; Carbonates; Alkalies; Carbonic Acid; Carbon Compounds, Inorganic; Lithium Compounds

Results Point of Contact

• Title: Elizabeth Streeten, MD
• Organization: University of Maryland School of Medicine

estreete@som.umaryland.edu

410-328-3335

Study Officials

• Elizabeth A Streeten, MD

  University of Maryland, College Park

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor of Medicine

Study Record Dates

• First Submitted: April 20, 2010
• First Posted: April 21, 2010
• Study Start: July 1, 2010
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: November 4, 2019
• Results First Posted: April 27, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)