Clinical trial NCT03344016: Multicenter Pheochromocytoma and Paraganglioma Evaluation
Official title: The MUPPET-study: Multicenter Pheochromocytoma and Paraganglioma Evaluation for Follow-up Screening, Genetics Sub-Typing, Therapy and Outcome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Pheochromocytoma
Paraganglioma
Lead sponsor: Ludwig-Maximilians - University of Munich
Sponsor class: OTHER
Collaborators: name: Technische Universität Dresden
name: Wuerzburg University Hospital
name: University of Zurich
name: Radboud University Medical Center
name: Lübeck University Clinic
name: Ludwig-Maximilians - University of Munich
First posted: 2017-11-17
Enrollment: 1148
Sex: ALL
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: To provide evidence whether strict follow-up will result in improvement in clinical outcome parameters as compared to standard care follow-up, patients upon inclusion into the study protocol will be randomized into two groups:

* Standard care follow-up group: Patients will receive an information leaflet (see appendix), which advises on recommended routine follow-up according to international guidelines.
* Special care follow-up group: In addition to the information leaflet patients will be actively contacted by the clinical center to increase the likelihood that patients meet recommended follow-up schedules.

Stratification will be done for inclusion criteria (newly diagnosed PPGL, previous history of PPGL, gene carrier, presence of malignant PPGL and center).
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: Target population:

Patients with (1) newly diagnosed or (2) past history of pheochromocytomas and paragangliomas (PPGL) or (3) carrier of genetic mutations in known PPGL susceptibility genes.

International multicenter prospective cohort study with randomized intervention (special care follow-up vs. standard care follow-up).

All patients will receive instructions about follow-up at the time point of study inclusion. Patients randomized to the standard care follow-up group will be advised to return annually for follow-up according to current routine practice (without active re-scheduling). In contrast, patients randomized to the special care follow-up group will also be advised to return annually for follow-up but these patients will be actively invited, re-scheduled and reminded by the centers to meet scheduled follow-up appointments.

Detailed description: The long-term goal of the research planned under this protocol is to reduce morbidity and mortality of patients with PPGLs by improving approaches for management, follow-up and therapy of affected patients. As a first step towards attaining this goal, the primary objective of this protocol is to investigate whether standardized follow-up results in improved long-term outcome in terms of less morbidity and mortality as compared. The central hypothesis is that pro-active, structured and periodic disease screening and management of patients at risk for developing PPGLs and other neoplasms can lead to earlier detection of tumors and reduce adverse outcomes associated with cardiovascular, metabolic and oncologic complications of the tumors than standard care follow-up. The underlying rationale is that establishing improved outcomes for patients at risk for PPGLs will enable evidence-based recommendations for disease follow-up and management, thereby establishing wider acceptance and use of outlined practices with ensuing improvements in the health and quality of life of affected patients and their families.

In addition to the primary objective directed at establishing whether standardized and structured follow-up of patients with an increased risk for new events of PPGL (recurrent tumor, new tumor, or metastases) will result in improved longterm outcome, this protocol will enable several secondary objectives to be addressed using clinical (e.g. age, mode of presentation), biochemical, metabolic and genetic characteristics. These include:

1. to identify prognostic markers of disease progression
2. to assess whether clinical presentation, cardiovascular, metabolic and biochemical phenotype, genetic background and tumor characteristics (location, size, recurrence, pathology) are useful for development of personalized follow-up strategies.
3. to investigate whether standardized follow-up affects quality of life

Eligibility criteria: Inclusion Criteria:

male and female patients (≥ 5 years of age), who fulfill one or more of the following criteria: (i) Patients with a newly diagnosed PPGL. (ii) Patients with a previous history of PPGLs. (iii) Carrier of genetic mutations known to predispose for the development of PPGLs.

All subjects must have read, understood and signed the informed consent form, before inclusion into the study protocol. Signed parental consent must be obtained for children with suspected PPGLs who are enrolled in the study.

Exclusion Criteria:

* Patients with impaired mental capacity that precludes informed consent.
* Pregnancy does not constitute criteria for exclusion from the protocol. However, in pregnant women no Clonidine testing, no PET scanning, MIBG scanning or contrast CT will be performed.
* Patients at risk from injury from the MRI magnet due to implantable metal or who suffer from anxiety in enclosed spaces are excluded from MRI.

Primary outcomes:
measure: Morbidity
timeFrame: 18 years
Secondary outcomes:
measure: Time to recurrence
timeFrame: 18 years
measure: Size of recurrent tumors
timeFrame: 18 years
measure: Numbers of metastases
timeFrame: 18 years
measure: Biomarker indices of disease burden
timeFrame: 18 years
measure: Metabolic parameter - blood glucose
timeFrame: 18 years
measure: Metabolic parameter - HbA1c
timeFrame: 18 years
measure: Metabolic parameter - cholesterol
timeFrame: 18 years
measure: Hormonal parameters
timeFrame: 18 years
measure: Blood pressure profiles
timeFrame: 18 years
measure: Cardiac function
timeFrame: 18 years
measure: Disease specific mortality
timeFrame: 18 years
measure: Overall mortality
timeFrame: 18 years
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: University Hospital Zurich
Study officials:
affiliation: University of Zurich
name: Felix Beuschlein, M.D.
role: PRINCIPAL_INVESTIGATOR
References: