Clinical trial NCT01111396: Longitudinal Investigation of Hippocampal Function and Morphology in Acute Lymphatic Leukemia (ALL) Patients Treated With Chemotherapy
Official title: Longitudinal Investigation of Hippocampal Function and Morphology in ALL Patients Treated With Chemotherapy: A Monocentric, Interdisciplinary Pilot Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Acute Lymphatic Leukemia
Keywords: ALL
GMALL 2003
Chemotherapy
Hippocampus
Lead sponsor: Technische Universität Dresden
Sponsor class: OTHER
Collaborators: name: Martin-Luther-Universität Halle-Wittenberg
First posted: 2010-04-27
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Consecutive patients of the Department of Internal Medicine at the Dresden University of Technology hospital, who are initially diagnosed of acute lymphatic leukemia (ALL) and included into the GMALL 2003 chemotherapy study. All treatment procedures and outcome measurements of the GMALL 2003 study (most importantly also the safety outcome measures) are regularly performed in the sub population of the present sub study. Inclusion and exclusion criteria are given below.

Brief summary: There are two regions in the adult brain that exhibit neuronal stem and progenitor cells, generating new neurons postnatally and throughout adulthood. One is the so called subventricular zone the other is the dentate gyrus of the hippocampus. Adult neurogenesis is a physiological process representing an important functional impact for certain brain areas, especially the hippocampus. The hippocampal formation plays an important role in long-term memory and spatial navigation. Inhibition of adult neurogenesis in mice by chemotherapy or radiation is followed by significant deficits in hippocampal memory functions while hippocampus-independent memory is unaffected.

Clinical trials had shown that chemotherapy and brain radiation lead to cognitive dysfunction. However, the exact mechanisms underlying this phenomenon are still unidentified.

The aim of our study is to investigate, whether the inhibition of adult neural stem cell proliferation in the hippocampus by intrathecal chemotherapy and/or cerebral radiation is responsible for treatment induced memory deficits. We will investigate patients suffering from acute lymphatic leukaemia (ALL) that receive prophylactic intrathecal chemotherapy and brain irradiation. The study represents a longitudinal investigation including a virtual "humanized" version of the morris-water-maze to test hippocampus dependent spatial memory, as well as MR-imaging for morphological (volumetry) and biochemical (spectroscopy) data.


Eligibility criteria: Inclusion Criteria:

* Initial diagnosis of acute lymphatic leukaemia (ALL)
* Treatment within the German Multicenter Adult ALL (GMALL 2003) therapy study
* Age 18 to 40 years
* Eligibility for performing study procedure
* Informed consent

Exclusion Criteria:

* Neuropsychiatric disorders
* Present contraindication for MRI investigation (e.g. pacemaker)

Primary outcomes:
measure: Hippocampal function measured with virtual water maze test
timeFrame: day 0
measure: Hippocampal function measured with virtual water maze test
timeFrame: day 9
measure: Hippocampal function measured with virtual water maze test
timeFrame: day 16
measure: Hippocampal function measured with virtual water maze test
timeFrame: day 52
measure: Hippocampal function measured with virtual water maze test
timeFrame: day 70
measure: Hippocampal function measured with virtual water maze test
timeFrame: week 36
Secondary outcomes:
measure: Hippocampal morphology measured by MRI
timeFrame: day 0
measure: Hippocampal morphology measured by MRI
timeFrame: day 29
measure: Hippocampal morphology measured by MRI
timeFrame: day 70
measure: Hippocampal morphology measured by MRI
timeFrame: week 36
measure: Peripheral blood cell count
timeFrame: day 0
measure: Peripheral blood cell count
timeFrame: day 26
measure: Peripheral blood cell count
timeFrame: day 46
measure: Peripheral blood cell count
timeFrame: day 71
measure: Peripheral blood cell count
timeFrame: week 16
measure: Peripheral blood cell count
timeFrame: week 22
measure: Peripheral blood cell count
timeFrame: week 30
measure: Peripheral blood cell count
timeFrame: week 41
measure: Peripheral blood count
timeFrame: week 52
measure: Bone marrow examination
timeFrame: day 0
measure: Bone marrow examination
timeFrame: day 26
measure: Bone marrow examination
timeFrame: day 46
measure: Bone marrow examination
timeFrame: day 71
measure: Bone marrow examination
timeFrame: week 16
measure: Bone marrow examination
timeFrame: week 22
measure: Bone marrow examination
timeFrame: week 30
measure: Bone marrow examination
timeFrame: week 41
measure: Bone marrow examination
timeFrame: week 52
Other outcomes:
Locations:
city: Dresden
country: Germany
facility: Dresden University of Technology University Hospital
Study officials:
affiliation: Technische Universität Dresden
name: Alexander Storch, MD
role: PRINCIPAL_INVESTIGATOR
References: