Symptoms and General Pathology

All Conditions

Behaviors and Mental Disorders

Neoplasms

Diseases and Abnormalities at or Before Birth

Rare Diseases

Syndrome

Autistic Disorder

Neurodevelopmental Disorders

Hamartoma

Hamartoma Syndrome, Multiple

Neoplasms, Multiple Primary

Neoplastic Syndromes, Hereditary

Genetic Diseases, Inborn

PTEN Hamartoma Tumor Syndrome

Patients diagnosed with PTEN Hamartoma Tumor Syndrome and a neurodevelopmental disorder including but not limited to autism spectrum disorder, attention-deficit disorder / attention-deficit hyperactivity disorder, speech language disorder(s), intellectual disability, global developmental delay, oppositional defiant disorder, and / or motor or developmental disorders.

Patients diagnosed with PTEN Hamartoma Tumor Syndrome

Siblings related to patients with diagnosis of PTEN Hamartoma Tumor Syndrome

Unrelated participants with no known genetic or neurodevelopmental disorder

Online survey measuring a variety of developmental domains including anxiety, motor, daily living skills, challenging behaviors, social communication, restrictive and repetitive behaviors, ADHD, executive functioning, mood, quality of life, and sleep

The purpose of this study is to develop a survey completed by parents, caregivers, or other informants that evaluates several important domains of functioning relevant to individuals with neurodevelopmental disorders, including autism spectrum disorder and people with genetic syndromes. Participation in this research will include assisting the research team in the development of the survey measures.

With greater understanding of the biology of PTEN Hamartoma Tumor Syndrome (PHTS), including patients with and without neurodevelopmental disorder (NDD) phenotypes, there is potential to develop novel personalized therapeutics. Given the recent observation that many PHTS patients with and without NDD have significant neurobehavioral manifestations, it will be crucial to broadly track a range of neurobehavioral domains as part of future trials. Unfortunately, there are few well-validated measures that would be appropriate for the full range of presentations in the PHTS population. Further, as a rare genetic syndrome, PHTS patients are geographically distributed making frequent data collection during research very difficult. Thus, the overarching aim of this proposal is to develop and validate an online neurobehavioral evaluation tool (NET) with caregiver-report survey scales and patient-completed webcam-collected performance measures that captures key neurobehavioral information. In partnership with patients, caregivers, and scientist-clinician experts, the study will develop, pilot test, and validate NET survey and performance measures. Specifically, at least 240 caregiver-patient pairs will be recruited (patient ages 4-24) from PHTS without NDD, PHTS with NDD, and controls (sibling and unrelated healthy controls). NET data will be collected at baseline, 1-month, and 4-month follow-up. Aim 1 will focus on the development and validation of brief, psychometrically-sound NET survey scales. Aim 2 will conduct group comparisons on NET measures. Aim 3 will use longitudinal data to evaluate short-term stability of NET survey scales and describe neurobehavioral change within and across study groups. The project will also explore the feasibility of performance measure collection, provide initial psychometric evaluation, and conduct a group comparison of performance measures. If the project aims are achieved, and future validation supports research and clinical use, the NET will be an efficient, reliable, valid, co-normed, multi-modal instrument, that, by virtue of online (at-home) administration, will decrease patient and family burden and increase the temporal resolution and power of future longitudinal studies and clinical trials.

Development and Validation of an Online Neurobehavioral Evaluation Tool for PTEN Patients

Development and Validation of an Online Neurobehavioral Evaluation Tool for PTEN Hamartoma Tumor Syndrome (PHTS)

Plan to upload deidentified data to Open Science Framework

Develop survey questions and scales related content areas for Social Communication Interactions. Social communication refers to the emergence of verbal and nonverbal skills, social interaction, and social cognition

Develop questions and survey scales related to content areas of activities of daily living. Activities of daily living are activities related to personal care. They include bathing or showering, dressing, getting in and out of bed or a chair, walking, using the toilet, and eating.

Develop survey and rating scales related to content areas for restrictive and repetitive behaviors. Restricted and repetitive behaviors and interests are among the three core symptoms of autism. They include repetitive movements with objects, repeated body movements such as rocking and hand-flapping, ritualistic behavior, sensory sensitivities and circumscribed interests

Develop survey questions and scales related to content areas for anxiety. Anxiety is what we feel when we are worried, tense or afraid - particularly about things that are about to happen, or which we think could happen in the future

Develop survey questions and scales related to content areas for motor skills.A motor skill is a function that involves specific movements of the body's muscles to perform a certain task. These tasks could include walking, running, or riding a bike. In order to perform this skill, the body's nervous system, muscles, and brain have

Develop survey questions and rating scales related to content areas for challenging behaviors.A person's behaviour can be defined as "challenging" if it puts them or those around them (such as their carer) at risk, or leads to a poorer quality of life. It can also impact their ability to join in everyday activities. Challenging behaviour can include: aggression. self-harm.

Develop survey questions and rating scales related to content areas for ADHD. Refers to the ongoing pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development.

Develop survey questions and rating scales related to content areas for executive functioning. Executive functioning and self-regulation skills are the mental processes that enable us to plan, focus attention, remember instructions, and juggle multiple tasks successfully.

Develop survey questions and rating scales related to content areas for mood. Focusing on particular feelings or a state of mind.

Develop survey questions and rating scales related to content areas for quality of life including family, financial, etc.

Develop survey questions and rating scales related to content areas for sleep patterns and behaviors.

University Hospital Southampton NHS Foundation Trust

John Carroll University

Infections

Respiratory Tract (Lung and Bronchial) Diseases

Influenza, Human

Arm contains all subjects; vaccination with Influvac Tetra will be administered at start of study, response will be measured in 7 and 21 days.

Tetravalent seasonal flu vaccination 2018/2019

Influvac Tetra

this study evaluates the cellular and humoral immune response to seasonal influenze vaccination in PTEN Hamartoma Tumor Syndrome. All subjects will be administered flu vaccination, half of the subjects will be control subjects.

Response of Immune System to Flu Vaccination in PHTS

Registering the Immune Response to a Flu Vaccination Challenge in PTEN Hamartoma Tumour Syndrome

Radboud University Medical Center

Digestive System Diseases

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Colorectal Neoplasms

Nasopharyngeal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Nasopharyngeal Diseases

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Cowden Syndrome

Bannayan-Riley-Ruvalcaba Syndrome

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Herbal and Botanical

Sirolimus

Temsirolimus

MTOR Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Immunosuppressive Agents

Immunologic Factors

Cola

There will be a clinic visit and colonoscopy at study entrance with standard of care sampling and assessment of polyps, including resection of concerning polyps. The investigators will also collect data on well-being via the SF-36 health survey (a validated questionnaire to help monitor this aspect given anecdotal patient-level reports of improvement while on therapy).

Study subjects will then begin sirolimus 2 mg by mouth daily for 1 year.

Laboratories will be checked at 4 days after initiation, at 2 weeks after initiation, then every 4 weeks for 3 months, then every 3 months to complete the year of therapy

Participants will have a clinic visit at 3, 6 and 9 months and include well-being assessment with the SF-36 health survey.

Participants will have a clinic visit with well-being assessment and perform colonoscopy at study closure at 12 months. The investigators will perform standard of care sampling and assessment of polyps, including resection of concerning polyps.

Use of sirolimus 2 mg by mouth daily for 1 year

Peter P Stanich, MD

Colon polyposis (the presence of multiple colon polyps) is very common with Cowden syndrome, as over 60% of patients have 50 or more polyps. In a previous clinical trial, some participants had reduction in the number of colon polyps with the use of the medication sirolimus for a very short time period. This study is investigating sirolimus and its effect on the number of colon polyps in patients with Cowden syndrome and polyposis over a 1 year period.

PTEN is a tumor suppressor gene that regulates the cell cycle through the phosphoinositide 3-kinase (PI3K)/Akt/mTOR pathway. When germline mutations in PTEN occur, the result is Cowden syndrome (or less commonly one of several related disorders collectively called the PTEN hamartoma tumor syndrome). This is characterized by the growth of hamartomas and a high risk of cancer in multiple organ systems. This includes colon polyps in 92.5% of Cowden syndrome patients and 64% with an estimated 50 or more polyps. Although outcomes of this are under reported, series suggest 20-38% of patients will receive colectomy.

Current clinical practice for Cowden syndrome is based on close surveillance for the development of cancers. Sirolimus (also known as rapamycin) is a specific inhibitor of mTOR that is FDA-approved for immunosuppression and use in several types of cancers as chemotherapy. It has also been used successfully in other hamartomatous syndromes including lymphangioleiomyomatosis. There is also a completed pilot clinical trial for adults with Cowden syndrome in which some had reduction in the number of colon polyps with the use of the medication sirolimus for a very short time period.

This will be an open-label pilot trial to determine whether sirolimus reduces colon polyp burden in Cowden syndrome. Sirolimus will be administered for one year. Colonoscopy with polyp estimation will be performed at trial entrance and at study completion.

Sirolimus for Cowden Syndrome With Colon Polyposis

Assessment of change in number of colon polyps. This will be assessed for each segment of colon (ascending, transverse, descending, sigmoid, rectum) and then aggregated into a total number of colon polyps. The entrance result will be compared to the final result for each participant.

Assessment of change in staging of colon polyps by using the International Society for Gastrointestinal Hereditary Tumors (InSIGHT) polyposis staging system. The InSight staging system divides colorectal polyposis into 5 progressive stages based on polyp number and size (Stage 0: \<20 polyps, all \<5 mm; Stage 1: 20-200 polyps, most \<5 mm, none, \>1 cm; Stage 2: 200-500 polyps, \<10 that are \>1 cm; Stage 3: 500-1000 polyps or any number if there are 10-50 that are \>1 cm and amenable to complete polypectomy; Stage 4: \>1000 polyps and/or any polyps grown to confluence and not amenable to simple polypectomy; any high-grade dysplasia or invasive cancer). The entrance result will be compared to the final result for each participant.

Assessment in change in overall health and quality of life as quantified by the SF-36 (Short Form) Health Survey. The SF-36 is a widely-used and standardized survey of participant responses to 36 questions that measures health-related quality of life. Each question has answers that are given a correlating score from 0 to 100, with a high score representing a more favorable health state. Through the combination of specific questions and averaging the scores, there are 8 scales (physical functioning, role limitations due to physical health, role limitations due to emotional problems, vitality, mental health, social functioning, bodily pain, and general health) that are reported with scores from 0 to 100, with a high score representing a more favorable health state. These can also be averaged into a physical component summary score and mental component summary score that is again from 0 to 100, with a high score representing a more favorable health state.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Development and Validation of an Online Neurobehavioral Evaluation Tool for PTEN Patients	NCT05671107	PTEN Hamartoma ...	NET	3 Years - 45 Years	John Carroll University
Response of Immune System to Flu Vaccination in PHTS	NCT03630523	PTEN Hamartoma ...	Influvac Tetra	18 Years -	Radboud University Medical Center
Sirolimus for Cowden Syndrome With Colon Polyposis	NCT04094675	PTEN Gene Mutat... PTEN Hamartoma ... PTEN Hamartoma ... Cowden Syndrome Bannayan Syndro... Bannayan Zonana... Polyposis	Sirolimus	18 Years - 80 Years	Ohio State University
Sirolimus for Cowden Syndrome With Colon Polyposis	NCT04094675	PTEN Gene Mutat... PTEN Hamartoma ... PTEN Hamartoma ... Cowden Syndrome Bannayan Syndro... Bannayan Zonana... Polyposis	Sirolimus	18 Years - 80 Years	Ohio State University

Spots Global Cancer Trial Database for phts

Every month we try and update this database with for phts cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for phts

Every month we try and update this database with for phts cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for phts cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.