Trial document




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  DRKS00006080

Trial Description

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Title

Cerebral hemodynamics after brachytherapy in pediatric patients with supratentorial low-grade astrocytoma or optic pathway glioma in patients with and without neurofibromatosis type I

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

Our study compares the cerebral hemodynamics of children and young adults after irradiation of the brain due to a benign brain tumor of the cerebrum or evolving from the optic nerve (pilocytic astrocytoma or optic nerve glioma). Using ultrasound, we compare two mechanisms of cerebral hemodynamics: Cerebral autoregulation keeps cerebral blood flow at constant levels irrespective of varying systemic blood pressure values. Neurovascular coupling leads to increased blood supply of particularly active brain areas.
Patients with neurofibromatosis type 1 are at special risk of developing a benign brain tumor especially of the optic nerve. These patients are also especially vulnerable to radiation damage. In our study we want to compare the cerebral hemodynamics of patients with and without neurofibromatosis type 1, and if interstitial irradiation has different effects on cerebral hemodynamics.

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Brief Summary in Scientific Language

Cerebral vasculopathy is a common late sequela after irradiation of the brain (Bitzer et al. 1995, Morris et al. 2009). Patients with neurofibromatosis type 1 are affected to a special degree (Grill 1999, Kortmann 2003). This also applies to children with direct irradiation of the tumor bed (brachytherapy). Vasculopathy of cerebral vessels can lead to various clinical symptoms. Arterial stenosis comes along with an increased risk of ischemic stroke and can lead to neovascularisation/Moya-Moya disease (Omura 1997, Serdaroglu 2000). Moreover, there is an increased risk of other vascular malformations and bleedings (Liu 2009, Poussaint 1995).
Cerebral circulation is regulated by several mechanisms. Cerebral autoregulation keeps cerebral blood flow at constant levels irrespective of varying systemic blood pressure values. Slow oscillations of systemic and cerebral blood flow occur spontaneously whereat cerebral oscillations are time-shifted to systemic oscillations in which the phase shift embodies functioning cerebral autoregulation (Kuo et al. 2003). Neurovascular coupling leads to increased blood supply of particularly active brain areas. For instance, visual stimulation leads to an increase of blood flow velocity in posterior brain areas. Both adaptive mechanisms can be evaluated by ultrasonic testing.
Ultrasonic testing of cerebral hemodynamics enables a functional and non-invasive evaluation of cerebral blood circulation beyond a morphological delineation of the vessels.
In our study we would like to compare the dynamic cerebral autoregulation and neurovascular coupling in patients with suprasellar low-grade astrocytoma or optic pathway glioma (with or without neurofibromatosis type 1) after brachytherapy during childhood. The aim of our study is to better understand the development of vascular damage after irradiation of the brain with special focus on patients with neurofibromatosis type 1.

Bitzer M, Topka H. Progressive cerebral occlusive disease after radiation therapy. Stroke. 1995 Jan;26(1):131-6.
Brzezinska R, Schumacher R. Diagnosis of elevated intracranial pressure in children with shunt under special consideration of transglobe sonography of the optic nerve. Ultraschall Med 2002;23(5):325-332.
Grill J, Couanet D, Cappelli C, Habrand JL, Rodriguez D, Sainte-Rose C, Kalifa C. Radiation-induced cerebral vasculopathy in children with neurofibromatosis and optic pathway glioma. Ann Neurol. 1999 Mar;45(3):393-6.
Kortmann RD, Timmermann B, Taylor RE, Scarzello G, Plasswilm L, Paulsen F, Jeremic B, Gnekow AK, Dieckmann K, Kay S, Bamberg M. Current and future strategies in radiotherapy of childhood low-grade glioma of the brain. Part II: Treatment-related late toxicity. Strahlenther Onkol. 2003 Sep;179(9):585-97.
Kreth FW, Faist M, RossnerR, Birg W, Volk B, Ostertag CB. The risk of interstitial radiotherapy of low-grade gliomas. Radiother Oncol. 1997 Jun;43(3):253-60.
Kuo TB, Chern CM, Yang CC, Hsu HY, Wong WJ, Sheng WY, Hu HH. Mechanisms underlying phase lag between systemic arterial blood pressure and cerebral blood flow velocity. Cerebrovasc Dis 2003;16:402-409.
Liu AK, Bagrosky B, Fenton LZ, Gaspar LE, Handler MH, McNatt SA, Foreman NK. Vascular abnormalities in pediatric craniopharyngioma patients treated with radiation therapy. Pediatr Blood Cancer. 2009 Feb;52(2):227-30.
Morris B, Partap S, Yeom K, Gibbs IC, Fisher PG, King AA. Cerebrovascular disease in childhood cancer survivors: A Children's Oncology Group Report. Neurology. 2009 Dec 1;73(22):1906-13.
Omura M, Aida N, Sekido K, Kakehi M, Matsubara S. Large intracranial vessel occlusive vasculopathy after radiation therapy in children: clinical features and usefulness of magnetic resonance imaging. Int J Radiat Oncol Biol Phys. 1997 May 1;38(2):241-9.
Poussaint TY, Siffert J, Barnes PD, Pomeroy SL, Goumnerova LC, Anthony DC, Sallan SE, Tarbell NJ. Hemorrhagic vasculopathy after treatment of central nervous system neoplasia in childhood: diagnosis and follow-up. AJNR Am J Neuroradiol. 1995 Apr;16(4):693-9.
Reinhard M, Roth M, Müller T, Czosnyka M, Timmer J, Hetzel A. Cerebral Autoregulation in Carotid Artery Occlusive Disease Assessed From Spontaneous Blood Pressure Fluctuations by the Correlation Coefficient Index. Stroke. 2003;34:2138-2144.
Rosengarten B, Molnar S, Trautmann J, Kaps M. Simultaneous VEP and transcranial Doppler ultrasound recordings to investigate activation-flow coupling in humans.
Serdaroğlu A, Simşek F, Gücüyener K, Oğuz A, Karadeniz C, Balibey M. Moyamoya syndrome after radiation therapy for optic pathway glioma: case report. J Child Neurol. 2000 Nov;15(11):765-7.
Tacke U, Karger D, Spreer J, Berlis A, Nikkhah G, Korinthenberg R. Incidence of vasculopathy in children with hypothalamic/chiasmatic gliomas treated with brachytherapy. Childs Nerv Syst. 2011 Jun;27(6):961-6. doi: 10.1007/s00381-010-1370-0. Epub 2011 Mar 17.

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Organizational Data

  •   DRKS00006080
  •   2014/04/17
  •   [---]*
  •   yes
  •   Approved
  •   144/14, Ethik-Kommission der Albert-Ludwigs-Universität Freiburg
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Secondary IDs

  •   U1111-1155-4914 
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Health Condition or Problem studied

  •   D33.0 -  Benign neoplasm: Brain, supratentorial
  •   Q85.0 -  Neurofibromatosis (nonmalignant)
  •   I67.9 -  Cerebrovascular disease, unspecified
  •   Y84.2 (ICD10) Radiological procedure and radiotherapy
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Interventions/Observational Groups

  •   Cerebral autoregulation (phase and gain) and neurovascular coupling (rate time, natural frequency, attenuation, gain) and simultaneous recording of visually-evoked potential (latency and amplitude of VEP) of children and young adults with history of interstitial radiotherapy due to a supratentorial low-grade astrocytoma or optic pathway glioma by a single-time dopplersonographic examination. Clinical data will be assessed by means of a questionnaire.
  •   Cerebral autoregulation (phase and gain) and neurovascular coupling (rate time, natural frequency, attenuation, gain) and simultaneous recording of visually-evoked potential (latency and amplitude of VEP) of children and young adults with supratentorial low-grade astrocytoma or optic pathway glioma without history of cerebral radiotherapy by a single-time dopplersonographic examination. Clinical data will be assessed by means of a questionnaire.
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Characteristics

  •   Non-interventional
  •   Other
  •   Non-randomized controlled trial
  •   Open (masking not used)
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  •   Other
  •   Basic research/physiological study
  •   Parallel
  •   N/A
  •   N/A
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Primary Outcome

Single-time dopplersonographic ultrasound examination of cerebral autoregulation (Phase
und Gain) as well as neurovascular coupling (rate time, natural frequency, attenuation, gain) and basic parameters of cerebral hemodynamics (pulsatility index, cerebral blood flow velocities of middle and posterior cerebral artery) at study inclusion.

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Secondary Outcome

At study inclusion, cinical data regarding diagnosis and treatment of the brain tumor, presence of neurofibromatosis type 1 and regarding cerebral vasculopathy, cerbrovascular events and cardiovascular risk factors will be assessed by a questionnaire. Clinical data will be correlated with the parameters of cerebral hemodynamics. Visually-evoked potentials are correlated with the parameters of neurovascular coupling.

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Actual
  •   2014/09/16
  •   32
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   6   Years
  •   25   Years
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Additional Inclusion Criteria

1.Children and young adults (age 6-25 years) with (patients) or without (control) a history of interstitial cerebral radiotherapy ("Seed") during childhood due to a supratentorial low-grade astrocytoma or glioma of the optic pathway
2. Written informed consent to the study by the patient/proband or accordingly the person having the care and custody of the child.

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Exclusion Criteria

1. No ultrasound window for transtemporal ultrasound. 2. history of external irradiation of the brain

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Addresses

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    • Zentrum für Kinder- und Jugendmedizin, Abteilung für Neuropädiatrie und Muskelerkrankungen
    • Mr.  Prof. Dr.  Rudolf  Korinthenberg 
    • Mathildenstr. 1
    • 79106  Freiburg
    • Germany
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    • Neurozentrum, Abteilung für Neurologie
    • Mr.  Prof. Dr.  Matthias  Reinhard 
    • Breisacher Str. 64
    • 79106  Freiburg
    • Germany
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    • Zentrum für Kinder- und Jugendmedizin, Abteilung für Neuropädiatrie und Muskelerkrankungen
    • Ms.  Dr.  Wibke  Janzarik 
    • Mathildenstr. 1
    • 79106  Freiburg
    • Germany
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    • Zentrum für Kinder- und Jugendmedizin, Abteilung für Neuropädiatrie und Muskelerkrankungen
    • Ms.  Dr.  Wibke  Janzarik 
    • Mathildenstr. 1
    • 79106  Freiburg
    • Germany
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Sources of Monetary or Material Support

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    • Zentrum für Kinder- und Jugendmedizin, Abteilung für Neuropädiatrie und Muskelerkrankungen
    • Mr.  Prof. Dr.  Rudolf  Korinthenberg 
    • Mathildenstr. 1
    • 79106  Freiburg
    • Germany
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Status

  •   Recruiting stopped after recruiting started
  •   2015/05/20
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.