Clinical trial NCT02308904: Reproductive Capacity and Iron Burden in Thalassemia
Official title: Reproductive Capacity and Association to Iron Burden and Chelation Patterns in Thalassemia Major Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: THALASSEMIA MAJOR
Keywords: Infertility
Thalassemia
Iron overload
Pituitary Iron Load
Oxidative Stress
REPRODUCTIVE CAPACITY AND ASSOCIATION TO IRON BURDEN AND CHELATION PATTERNS IN THALASSEMIA MAJOR PATIENTS
Lead sponsor: UCSF Benioff Children's Hospital Oakland
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
First posted: 2014-12-04
Enrollment: 59
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The improved long-term survival of thalassemia major (TM) patients has resulted in increased focus on the ability to preserve fertility. While the association of iron toxicity with vital organ dysfunction, heart and liver, has been extensively investigated, the correlation of reproductive capacity and extent of iron overload is not well understood. Despite remarkable progress in methodology for prediction of reproductive status and intervention for preserving fertility, implementation in thalassemia is lacking.

The investigators hypothesize that iron toxicity to the anterior pituitary occurring in the process of transfusional iron loading is directly associated with a decline in gonadal function. The investigators expect pituitary MRI measurements of iron deposition as well as markers of oxidative damage to correlate with the functional studies of pituitary-gonadal axis performed in this study. This cross sectional study will examine the relation of pituitary iron deposition and pituitary volume; serum iron and oxidative stress measures, liver iron concentration (LIC), cardiac iron and chelation adequacy with pituitary and gonadal reproductive hormone levels (and spermatogenesis in adult male patients), in order to better define the association of iron burden and chelation patterns with fertility potential, in thalassemia patients with iron overload. The study will assess whether the current chelation treatment regimens, in particular during the pubertal developmental age, are adequate for preserving fertility and could lead to improved chelation routines for preventing the high prevalence of compromised fertility. In addition, by utilizing state-of-the-art markers for fertility status, findings from this study may improve current methods for screening for hypogonadism and reproductive potential and allow earlier intervention.

The investigators propose to examine 26-30 patients, 12 years and older, with measures of fertility potential, and correlate them to their current iron burden parameters and to the cumulative iron effect as indicated by past iron overload patterns and chelation history.


Eligibility criteria: Inclusion Criteria:

* Transfusion-dependent\* females and males with thalassemia (any genotype) who are 12 to 45 years of age.
* History of at least 5 years of chronic transfusion (defined as ≥ 8 transfusions/year) (Age of initiation of transfusions does not matter)
* Any pubertal stage.
* Liver iron evaluated by SQUID, MRI or liver biopsy within 12 months prior to enrollment in the study.
* Need to be able to stop hormonal therapy for 3 weeks (males) and one month (females) prior to study enrollment.

Exclusion Criteria:

* Pregnant or lactating during study enrollment
* Unable to obtain liver iron concentration within 12 months prior or 6 months after study entry.

Primary outcomes:
measure: Laboratory studies for pituitary and gonadal function and for iron level measures
timeFrame: Up to 12 months
Secondary outcomes:
measure: Retrospective analysis of annual LIC and of type and dose of iron chelation agent in the parallel time period
timeFrame: Up to 12 months
Other outcomes:
measure: Pituitary MRI and Male: Semen analysis
timeFrame: Up to 12 months
Locations:
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital Oakland
state: California
Study officials:
affiliation: UCSF Benioff Children's Hospital Oakland
name: Sylvia T Singer, MD
role: PRINCIPAL_INVESTIGATOR
References: