Neoplasms

All Conditions

Rare Diseases

Carcinoid Tumor

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Dihydroxyphenylalanine

Serotonin

Participants who undergo extended evaluation for disease at NIH

Participants who do not undergo extended screening or evaluation for disease at NIH

[18F]-DOPA

Joanne Forbes, C.R.N.P.

Stephen A Wank, M.D.

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

This study will evaluate members in families with a history of small bowel carcinoid cancer to study the natural history of those family members that have the disease, determine ways to improve early detection by performing surveillance on those at risk but without disease and to identify the gene(s) that may cause the tumors. Familial carcinoid tumors usually originate in hormone-producing cells that line the small intestine or other cells of the digestive tract. The tumors are slow-growing and usually take many years before they cause symptoms. It is known that these tumors occur more often in some families and are then passed from one generation to the next by inherited genes.

Members of families, including all siblings and offspring in which two or more immediate blood relatives have had small bowel carcinoid tumors are eligible for this study. In some cases unaffected spouses of family members diagnosed with carcinoid cancer are also requested to participate by donating a sample of blood only.

Participants undergo a medical evaluation every 3 years during a 3- to 5-day hospital stay at the NIH Clinical Center. All participants have a personal and family medical history obtained and undergo a physical examination, blood and urine tests.

People who already have a small bowel carcinoid tumor or are at risk of developing a carcinoid tumor have some or all of the following procedures to determine the presence of carcinoid tumor and its (omit next two words- location or) spread to other areas of the body:

* Video Capsule Endoscopy: Visualization of the gastrointestinal tract by ingesting a disposable, "vitamin-pill sized" video capsule that has its own camera and light source.
* CT of the chest abdomen and pelvis with oral and IV contrast : X-ray examination of the chest, abdominal and pelvis organs.
* 18 FDOPA Positron emission tomography (PET) with CT for localization: Nuclear imaging scan to look at tumor activity.
* MRI Liver with contrast - to determine if disease has spread to liver
* Gallium 68 PET/CT-limited to individuals that have residual tumor.
* Clinical and research blood work

Should mid gut carcinoid tumors be found every participant will be assisted in determine what the best course of treatment will be for them.

...

Study Description:

This study is designed as a prospective evaluation for diagnostic screening, genotyping and natural history of participants belonging to kindreds with familial carcinoid tumor.

Objectives: Primary Objective:

Study the natural history of familial carcinoid tumors: incidence, age of onset, symptoms, the appropriate diagnostic (biochemical and imaging) modalities, location, histology and metastatic potential of the tumors, metabolic sequelae of the tumor, and clinical and biochemical prognostic factors.

Secondary Objectives:

* Screen for occult disease and determine whether early detection affects the natural history of the disease.
* Compare the sensitivity and specificity of various imaging tomography (CT) with IV contrast and oral Volumen, 18FDOPA PET/CT scan, \[68Ga\] DOTATATE PET/CT scan and endoscopic modalities for diagnosing and following carcinoid tumors.
* Collect tumor specimens for histologic evaluation, culturing of intestinal organoids, and genotyping (including DNA and RNA sequencing).
* Sequester DNA from peripheral blood for genotyping (including sequencing) with the intention of localizing a susceptibility gene/s responsible for the familial occurrence of the disease.

Natural History of Familial Carcinoid Tumor

Incidence, age of onset, symptoms, the appropriate diagnostic (biochemical and imaging) modalities, location, histology and metastatic potential of the tumors, metabolic sequelae of the tumor, and clinical and biochemical prognostic factors

Enrollment of a sufficient number of subjects to allow for the determination of sensitivity and specificity for each imaging and endoscopic modality to show statistically significant superiority for one modality relative to the others

Determination of the gene mutation responsible for the disease in each family

Sufficient number of tumors collected to correlate disease grade with natural history of disease and assess the variability in disease grade

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Annemiek Walenkamp, MDPhD

The objective of this observational laboratory study is to measure the correlation between 5-hydroxyindolacetic acid (5-HIAA) in platelet rich plasma and 5-HIAA in 24-hours urine collection in adult patients with a serotonin-producing neuro-endocrine tumor. Plasma and urine of included patients are collected and 5-HIAA values are measured with LCMS-MS and analysed.

In midgut NETs serotonin production is most prominent. Patients with NETs producing excessive serotonin can develop carcinoid syndrome. Serotonin is a product of the 'tryptophan pathway'. Serotonin is metabolized in 5-hydroxyindolacetic acid (5-HIAA) and then excreted with urine. 5-HIAA in 24-hour urine collection is one of the parameters used for follow up in patients with a serotonin-producing neuroendocrine tumor. This measurement has some disadvantages; it could be stressful, the collection is not always precisely, furthermore the collection could be problematic, for example in patients with diarrhea.

Since October 2013 it is possible, because of a better measurement sensitivity, to measure reliably 5-HIAA in platelet rich plasma (PRP) by isotope-dilution massa-spectrometer (LCMS-MS). Recent publications show that 5-HIAA measured in PRP could have an additive value in diagnosis and follow up of patients with serotonin-producing NET.

Objective:

The primary objective is to measure the correlation between 5-HIAA in PRP and 5-HIAA in 24-hours urine collection in adult patients with a serotonin-producing neuro-endocrine tumor.

Secondary objective is to determine if increase or decrease of 5-HIAA in plasma is associated with disease progression.

Study design:

This is an observational laboratory study. Plasma and urine of included patients and collected in standard health care, are selected and the 5-HIAA's are measured with LCMS-MS. Also age, sex, diagnosis and clinical course of the patients will be collected from the medical record.

Study population:

In this study the investigators will use blood and urine of 60 patients with serotonin-producing neuro-endocrine tumors.

Main study parameters/endpoints:

The main endpoint of this study is the correlation between 5-HIAA in PRP and 5-HIAA in 24-hour urine collection. Secondary endpoint is the correlation between 5-HIAA in PRP and course of the disease, determined by CT-scan (if applicable).

5-HIAA in Urine Versus 5-HIAA in Plasma Patients With a Serotonin Producing Neuroendocrine Tumor'

'5-HIAA in Urine Versus 5-HIAA in Plasma in Patients With a Serotonin Producing Neuroendocrine Tumor'

the course of the disease according to the course of 5-HIAA in plasma

University Medical Center Groningen

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Breast Neoplasms

Hot Flashes

Breast Diseases

Skin Diseases

Psychotropic Drugs

Amino Acids

Glycine

Tryptophan

Antidepressive Agents

Phenylalanine

Arginine

Alanine

Leucine

Cysteine

Lysine

Serine

Histidine

Tyrosine

Threonine

Proline

Methionine

Valine

Isoleucine

Half-strength tryptophan depletion drink used as a control

L-alanine (5.5g), L-arginine (4.9g), L-cysteine (2.7g), glycine (3.2g), L-histidine (3.2g), L-isoleucine (8.0g), L-leucine (13.5g), L-lysine (11.0g), L-methionine (3.0g), L-phenylalanine (5.7g), L-proline (12.2g), L-serine (6.9g), L-threonine (6.9g), L-tyrosine (6.9g), L-valine (8.9g)

Acute tryptophan depletion

L-alanine (1.4g), L-arginine (1.2g), L-cysteine (0.7g), glycine (0.8g), L-histidine (0.8g), L-isoleucine (2.0g), L-leucine (3.4g), L-lysine (2.8g), L-methionine (0.8g), L-phenylalanine (1.4g), L-proline (3.1g), L-serine (1.7g), L-threonine (1.7g), L-tyrosine (1.7g), L-valine (2.2g), and fillers (7.95g).

Half-strength tryptophan depletion (Control)

Janet S Carpenter, PhD

The purpose of this proposal is to improve our understanding of the role of tryptophan and serotonin in hot flashes. The main hypothesis is that alterations in tryptophan and serotonin levels are involved in the induction of hot flashes in women with breast cancer and genetic variations in the serotonin receptors and transporters also play a role.

Among women with breast cancer, hot flashes are a frequent, severe and bothersome symptom. For this group, hot flashes are negatively related to mood, affect, and daily activities and can compromise compliance with life-saving medications (e.g., tamoxifen). Over 60% of breast cancer survivors report hot flashes, with 59% stating they are extremely severe and 44% reporting them to be extremely bothersome. Unfortunately, limitations in our understanding of hot flash physiology limit clinicians' abilities to fully treat this symptom. Although the current non-hormonal treatment of choice for hot flashes after breast cancer targets the central serotonin system (e.g., paroxetine, venlafaxine), the role of serotonin in hot flashes has not been directly tested. Because the effectiveness of these agents has been based largely on improvement in subjective reporting of hot flashes, it is not clear whether benefits are due to physiological effects on hot flashes or due to improvements in mood or other related symptoms. In addition, these and other currently available treatments are not acceptable, appropriate, or effective for all women with breast cancer. Understanding the physiological mechanisms involved in hot flashes after breast cancer will enable us to develop more targeted behavioral and/or pharmacological therapies to be used in lieu of, or in addition to, currently available therapies so that we can eradicate hot flashes and improve the quality of life for women with breast cancer.

Results implicating direct effects of tryptophan and serotonin on objective hot flashes will help guide the development of improved interventions for alleviating hot flashes in women with breast cancer. These interventions may target the central serotonin system either behaviorally (e.g., diet) or pharmacologically (e.g., alternative drug therapeutics). If direct manipulation of tryptophan and serotonin does not affect hot flashes, these findings will be equally as useful in guiding future research on non-serotonin related etiologies and interventions. Findings from this study will ultimately be used to eradicate hot flashes as a frequent, severe and bothersome breast cancer treatment related condition, thereby, improving quality of life for all women with breast cancer.

The Role of Serotonin in Hot Flashes After Breast Cancer

Mean serum tryptophan levels (blood draw) at the end of the nadir period.

Mean of the 24 hour monitoring sessions for each patient based on one 24 hour monitoring session after each intervention using an electronic monitor.

Indiana University School of Medicine

Janet Carpenter, PhD, RN

Full Strength Acute Tryptophan Depletion

Half-Strength Tryptophan Depletion - Control

Consented subjects in the entire sample were randomized to one of two groups for the cross-over design study. One group of subjects received a full-strength tryptophan depletion drink during week 1 followed by a half-strength (control) drink week 2. The other group of subjects received a half-strength tryptophan depletion (control) drink during week 1 followed by a full-strength drink week 2.

The final analysis combined groups to compare full strength versus control.

Entire Sample

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Janet S. Carpenter

The number of subjects with complete serum data for both arms of the study were analyzed.

Serum Tryptophan Levels

Subjects with completed hot flash data during both arms of study.

Objective Subject Hot Flash Frequency

Subjects were randomized to receive both a full-strength acute tryptophan depletion drink and half-strength tryptophan depletion drink (control). Some participants received the full-strength drink first for week 1 and then crossed-over to the half-strength (control) drink for week 2; the other participants received the half-strength (control) drink for week 1 and then crossed over to the full-strength drink for week 2.

Full Strength Acute Tryptophan Depletion and Control

Week 1

Week 2

This study will evaluate members in families with a history of small bowel carcinoid cancer to study the natural history of those family members that have the disease, determine ways to improve early detection by performing surveillance on those at risk but without disease and to identify the gene(s) that may cause the tumors. Familial carcinoid tumors usually originate in hormone-producing cells that line the small intestine or other cells of the digestive tract. The tumors are slow-growing and usually take many years before they cause symptoms. It is known that these tumors occur more often in some families and are then passed from one generation to the next by inherited genes.

Members of families, including all siblings and offspring in which two or more immediate blood relatives have had small bowel carcinoid tumors are eligible for this study. In some cases unaffected spouses of family members diagnosed with carcinoid cancer are also requested to participate by donating a sample of blood only.

Participants undergo a medical evaluation every 3 years during a 3- to 5-day hospital stay at the NIH Clinical Center. All participants have a personal and family medical history obtained and undergo a physical examination, blood and urine tests.

People who already have a small bowel carcinoid tumor or are at risk of developing a carcinoid tumor have some or all of the following procedures to determine the presence of carcinoid tumor and its (omit next two words- location or) spread to other areas of the body:

* Video Capsule Endoscopy: Visualization of the gastrointestinal tract by ingesting a disposable, "vitamin-pill sized" video capsule that has its own camera and light source.
* CT of the chest abdomen and pelvis with oral and IV contrast : X-ray examination of the chest, abdominal and pelvis organs.
* 18 FDOPA Positron emission tomography (PET) with CT for localization: Nuclear imaging scan to look at tumor activity.
* MRI Liver with contrast - to determine if disease has spread to liver
* Gallium 68 PET/CT-limited to individuals that have residual tumor.
* Clinical and research blood work

Should mid gut carcinoid tumors be found every participant will be assisted in determine what the best course of treatment will be for them.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Natural History of Familial Carcinoid Tumor	NCT00646022	Carcinoid	[18F]-DOPA	18 Years -	National Institutes of Health Clinical Center (CC)
5-HIAA in Urine Versus 5-HIAA in Plasma Patients With a Serotonin Producing Neuroendocrine Tumor'	NCT02507908	Neuroendocrine ...		18 Years -	University Medical Center Groningen
The Role of Serotonin in Hot Flashes After Breast Cancer	NCT00228943	Breast Cancer	Acute tryptopha... Half-strength t...	18 Years -	Indiana University
Natural History of Familial Carcinoid Tumor	NCT00646022	Carcinoid	[18F]-DOPA	18 Years -	National Institutes of Health Clinical Center (CC)
The Role of Serotonin in Hot Flashes After Breast Cancer	NCT00228943	Breast Cancer	Acute tryptopha... Half-strength t...	18 Years -	Indiana University
Natural History of Familial Carcinoid Tumor	NCT00646022	Carcinoid	[18F]-DOPA	18 Years -	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for serotonin

Every month we try and update this database with for serotonin 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 serotonin

Every month we try and update this database with for serotonin 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 serotonin 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.