Multicenter Pheochromocytoma and Paraganglioma Evaluation (MUPPET)

The MUPPET-study: Multicenter Pheochromocytoma and Paraganglioma Evaluation for Follow-up Screening, Genetics Sub-Typing, Therapy and Outcome

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.

Study Overview

• Status: Recruiting
• Conditions: Pheochromocytoma; Paraganglioma
• Intervention / Treatment: Other: Contact by clinical center

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

• Study Type: Interventional
• Enrollment (Anticipated): 1148
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Felix Beuschlein, M.D.; Phone Number: +41 44 255 36 25; Email: felix.beuschlein@usz.ch
• Study Contact Backup: Name: Martin Reincke, M.D.; Phone Number: +49 89 4400 52100; Email: martin.reincke@med.uni-muenchen.de

Study Locations

• Switzerland
  • Zurich, Switzerland, 8091
    • Recruiting
    • University Hospital Zurich
    • Contact: Felix Beuschlein, M.D.; Phone Number: +41 44 255 36 25; Email: felix.beuschlein@usz.ch
    • Contact: Martin Reincke, M.D.; Phone Number: +49 89 4400 52100; Email: martin.reincke@med.uni-muenchen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard care follow-up group; Patients will receive an information leaflet (see appendix), which advises on recommended routine follow-up according to international guidelines.
Active Comparator: 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.	Other: Contact by clinical center; Patients will be acitvely contacted by the clinical center for follow-up procedure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morbidity	to investigate whether standardized follow-up for patients at risk for PPGL improves long-term outcome	18 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to recurrence	Time to recurrence	18 years
Size of recurrent tumors	Size of recurrent tumors	18 years
Numbers of metastases	Numbers of metastases	18 years
Biomarker indices of disease burden	Surrogate biomarker indices of disease burden (such as hormonal measures)	18 years
Metabolic parameter - blood glucose	fasting blood glucose	18 years
Metabolic parameter - HbA1c	Hb1Ac	18 years
Metabolic parameter - cholesterol	fasting cholesterol (total, LDL, HDL)	18 years
Hormonal parameters	hormonal profiles including metanephrines, normetanephrines and metoxytyramine (that will allow for sub-group specification of PPGLs)	18 years
Blood pressure profiles	Measurement of 24h blood pressure and ambulatory blood pressure measurments	18 years
Cardiac function	Leftventricualr ejection fraction	18 years
Disease specific mortality	Disease specific mortality	18 years
Overall mortality	Overall mortality	18 years

Collaborators and Investigators

• Sponsor: Felix Beuschlein
• Collaborators: Radboud University Medical Center; University of Zurich; Ludwig-Maximilians - University of Munich; Technische Universität Dresden; Wuerzburg University Hospital; Lübeck University Clinic
• Investigators: Principal Investigator: Felix Beuschlein, M.D., University of Zurich

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2017
• Primary Completion (Anticipated): November 1, 2035
• Study Completion (Anticipated): November 1, 2040

Study Registration Dates

• First Submitted: November 2, 2017
• First Submitted That Met QC Criteria: November 10, 2017
• First Posted (Actual): November 17, 2017

Study Record Updates

• Last Update Posted (Actual): July 9, 2020
• Last Update Submitted That Met QC Criteria: July 7, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Pheochromocytoma; Paraganglioma
• Other Study ID Numbers: 742-16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No