Analysis of Plasma for Diagnosis and Follow-up of Neurofibromatosis Type 1

The purpose of this study is to find blood plasma based biomarkers of disease progression in neurofibromatosis type 1 (NF1). NF1 is associated with the development of benign cutaneous tumors as well as a variety of malignancies. Analysis of plasma DNA and chemical composition may provide tools for diagnosis and follow-up of NF1. The hypothesis of the study is that NF1-associated tumor burden and malignant transformation of tumors can be detected in plasma. To test this hypothesis, Finnish patients with NF1 are recruited and blood sample is taken. Blood plasma is separated and analyzed chemically. DNA is then also extracted and quantified.

Study Overview

• Status: Unknown
• Conditions: Neurofibromatosis 1
• Intervention / Treatment: Other: Blood sample

Detailed Description

Neurofibromatosis type 1 (NF1) is a dominant hereditary multiorgan disease that causes both benign cutaneous neurofibromas and malignant tumors. Timely detection of malignant transformation in NF1 tumors is of great clinical importance. Also methods to easily monitor individual's overall tumor burden would be useful. Blood plasma is collected from NF1 patients and age- and gender-matched controls. The samples are stored at -80 C until analysis. Free circulating plasma DNA is extracted and quantified using commercial reagents. Also a previously described chemical detection method to observe overall changes in plasma composition is utilized. The analysis results are compared between NF1 patients and healthy controls, and also correlated with NF1 tumor burden and diagnosis of malignancy during five-year follow-up.

• Study Type: Observational
• Enrollment (Anticipated): 100

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients visiting Turku Neurofibromatosis Centre (Finland) for care of their disease. Controls are healthy volunteers from Turku area.

Description

Inclusion Criteria:

• Finnish-speaking
• 18-85 years old
• For NF1 group: Diagnosis of type 1 neurofibromatosis and visit to Turku Neurofibromatosis Centre
• For control group: Suitable as an age- and gender-matched control for some of the NF1 patients

Exclusion Criteria:

• Non-Finnish-speaking
• For control group: diagnosis of neurofibromatosis type 1 or cancer

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Neurofibromatosis 1; 10 mL venous blood sample taken from patients with type 1 neurofibromatosis	Other: Blood sample; 10 mL venous blood sample for analysis of plasma
Control; 10 mL venous blood sample taken from age- and gender-matched healthy controls	Other: Blood sample; 10 mL venous blood sample for analysis of plasma

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ability of free circulating plasma DNA concentration and unspecific chemical detection method to predict overall tumor burden	Tumor burden assessed by clinician on a four-level scale: 1 = 0-5 neurofibromas, 2 = 6-99 neurofibromas, 3 = 100-500 neurofibromas, 4 = over 500 neurofibromas	Up to 5 years
Ability of free circulating plasma DNA concentration and unspecific chemical detection method to predict clinical diagnosis of malignancy	Information on clinical diagnoses is obtained from patient records	Up to 5 years

Collaborators and Investigators

• Sponsor: Juha Peltonen
• Investigators: Principal Investigator: Juha Peltonen, Professor, University of Turku

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: January 15, 2016
• First Submitted That Met QC Criteria: February 8, 2016
• First Posted (Estimate): February 11, 2016

Study Record Updates

• Last Update Posted (Estimate): February 11, 2016
• Last Update Submitted That Met QC Criteria: February 8, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Genetic Diseases, Inborn; Neuromuscular Diseases; Neurodegenerative Diseases; Neoplasms, Nerve Tissue; Peripheral Nervous System Diseases; Nervous System Neoplasms; Heredodegenerative Disorders, Nervous System; Neoplastic Syndromes, Hereditary; Nerve Sheath Neoplasms; Neurocutaneous Syndromes; Peripheral Nervous System Neoplasms; Neurofibromatoses; Neurofibromatosis 1; Neurofibroma
• Other Study ID Numbers: 141-1801-2015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Molecular biology results and relevant clinical information will be shared along publication. Some clinical information is subject to privacy issues and cannot be shared.