Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Nervous System Diseases

Gland and Hormone Related Diseases

Musculoskeletal Diseases

Heart and Blood Diseases

Digestive System Diseases

Rare Diseases

Syndrome

Melanoma

Prostatic Neoplasms

Pituitary Diseases

Neuroendocrine Tumors

Acromegaly

Cardiac Complexes, Premature

Pituitary Neoplasms

ACTH-Secreting Pituitary Adenoma

Pituitary ACTH Hypersecretion

Dumping Syndrome

Adenoma

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Hypothalamic Diseases

Brain Diseases

Central Nervous System Diseases

Endocrine System Diseases

Bone Diseases

Bone Diseases, Endocrine

Endocrine Gland Neoplasms

Hypothalamic Neoplasms

Supratentorial Neoplasms

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Neoplasms, Glandular and Epithelial

Postgastrectomy Syndromes

Stomach Diseases

Gastrointestinal Diseases

Postoperative Complications

Neuroendocrine Tumor

ACTH-secreting Pituitary Adenoma

Neuroepithelioma

Anti-Dyskinesia Agents

All Drugs and Chemicals

Gastrointestinal Agents

Cardiotonic Agents

Cabergoline

Pasireotide

Lactitol

Somatostatin

Hormones

Hormone Antagonists

Antiparkinson Agents

Dopamine

Dopamine Agonists

Dopamine Agents

Neurotransmitter Agents

0.3mg, 0.6mg and 0.9mg. Doses to be taken BID or TID, dependent on parent study guidelines. Cabergoline may be combined in this arm for Cushing's Disease and Acromegaly patients.

10mg, 20mg, 40mg and 60mg. All doses to be taken q28days. Strength is dependent on parent study guidelines.

Administered subcutaneously in strengths 0.3mg, 0.6mg and 0.9mg. Doses to be taken BID or TID, dependent on parent study guidelines.

Cabergoline tablet 0.5mg or 1.0mg taken by mouth once daily may be combined with subcutaneous formulation of pasireotide for Cushing's Disease or Acromegaly. Dose is dependent on parent study guidelines.

Long Acting Release is administered by monthly injection. The strengths are 10mg, 20mg, 40mg and 60mg. All doses to be taken q28days. Strength is dependent on parent study guidelines.

Recordati

The purpose of this study is to allow continued use of pasireotide in patients who are on pasireotide treatment in a Novartis-sponsored study and are benefiting from the treatment as judged by the investigator.

This is a multi-center, open label, phase IV study to provide continued supply of pasireotide to patients being treated in a current Novartis-sponsored study and who are benefiting from treatment with pasireotide alone or in combination with another treatment for Cushing's Disease and Acromegaly . Eligible patients are to be consented and can then continue treatment with pasireotide alone or in combination with another treatment for Cushing's Disease and Acromegaly in this protocol. All patients at their scheduled visits will have drug dispensing information and reported adverse events and serious adverse events collected.

A patient will reach the end of study when pasireotide treatment is permanently discontinued and the end of treatment visit has been performed. All patients must be followed up for safety evaluations for 3 months following the last dose of pasireotide LAR treatment and for 1 month following the last dose of pasireotide s.c. treatment.

The study is expected to remain open for approximately 10 years or until such time that enrolled patients no longer need treatment with pasireotide or are able to obtain commercial supply according to local regulations for their medical condition.

Study to Allow Access to Pasireotide for Patients Benefiting From Pasireotide Treatment in Novartis-sponsored Studies

An Open Label, Multi-center Pasireotide Roll-over Protocol for Patients Who Have Completed a Previous Novartis-sponsored Pasireotide Study and Are Judged by the Investigator to Benefit From Continued Pasireotide Treatment

Collect long term safety data, i.e. SAEs and AEs. SAES will be reviewed and reported as part of the regular pharmacovigilance activities.

Clinical benefit rate as defined by Investigator based on the patients 24 hour Urinary Free Cortisol results.

RECORDATI GROUP

Nutritional and Metabolic Diseases

Behaviors and Mental Disorders

Esophageal Neoplasms

Nutrition Disorders

Gastroparesis

Feeding and Eating Disorders

Paralysis

Neurologic Manifestations

Mental Disorders

Psychotic Disorders

Esophageal Cancer

Hypoglycemic Agents

Pharmaceutical Solutions

Anti-Infective Agents

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Antineoplastic Agents

Antipyretics

Insulin

Insulin, Globin Zinc

Glucagon-Like Peptide 1

Sulfasalazine

Octreotide

Acetaminophen

Analgesics, Non-Narcotic

Antineoplastic Agents, Hormonal

Anti-Inflammatory Agents, Non-Steroidal

50mcg octreotide acetate by subcutaneous injection 10 minutes prior to a 400kcal mixed meal challenge

Octreotide Acetate

Equivalent volume of 0.9% saline by subcutaneous injection 10 minutes prior to a 400kcal mixed meal challenge

Saline Solution

Paracetamol 1g by mouth consumed with a 400kcal mixed meal challenge

Paracetamol

1g sulfasalazine by mouth consumed with a 400kcal mixed meal challenge

Biopsy from the second part of the duodenum taken at routine endoscopic surveillance, undertaken for another clinical indication.

Duodenal biopsy

John V Reynolds, MD FRCS

Carel W le Roux, FRCP FRCPath PhD

The incidence of oesophagogastric cancer has increased by 400% since the 1970s in Ireland and the United Kingdom. In addition, refinement of perioperative management and the now widespread use of multimodal protocols for patients with locally advanced disease have significantly improved outcomes for patients with oesophagogastric cancer treatable with curative intent. Despite significant advances in chemoradiotherapy, surgical resection remains the primary curative option.

Unintentional weight loss and nutritional complications represent serious concerns for patients after radical resection, even among those who remain free from recurrent disease in the long-term. A study from the Swedish Esophageal and Cardia Cancer Registry reported a mean three year weight loss of 10.8% among disease-free patients, with 33.8% of this cohort demonstrating malnutrition at three years post-oesophagectomy.

Mechanisms contributing to weight loss for disease-free patients after upper gastrointestinal surgery are poorly understood, however an association between increasing magnitude of weight loss and the presence of increased satiety is described. Our recent studies at SJH have demonstrated four fold elevated postprandial satiety gut hormone concentrations after oesophagectomy, compared with baseline preoperative values. Postprandial gut hormone levels correlate significantly with postprandial symptoms and altered appetite at 3 months postoperatively, and with body weight loss at 2 years postoperatively. However, the mechanism leading to exaggerated postprandial gut hormone production after upper gastrointestinal surgery is poorly understood, limiting targeted therapeutic options.

In this study, we aim to characterise the role of altered nutrient transit and enteroendocrine cell function in the pathophysiology of excessive post-prandial gut hormone responses after upper gastrointestinal surgery. To do this, we will measure the gut hormone response to a standardised 400 kcal meal, as per previous studies, while concurrently assessing gastrointestinal transit time, and enteroendocrine cell morphology and function. In this way, we will determine whether the magnitude of the postprandial gut hormone response correlates with the rate of nutrient transit into the enteroendocrine L-cell rich small intestine, and whether enteroendocrine cell adaptation occurs after oesophagectomy.

Furthermore, we have previously observed that gut hormone suppression using octreotide is associated with increased ad libitum among subjects after upper gastrointestinal cancer surgery (Elliott JA et al, Annals of Surgery, 2015). The mechanism of action of octreotide may relate to SSTR-5-mediated negative feedback to the enteroendocrine L-cell, but this medication may additionally reduce enteroendocrine L-cell responses through its inhibitory effect on gastrointestinal motility - reducing the rapidity with which nutrients are delivered to the small intestine - and small intestinal nutrient sensing via inhibition of the Na+-dependent glucose transporter SGLT-18-10. Through conduction of this double-blind, randomised, placebo-controlled crossover study, we aim to establish the mechanism of action of octreotide-mediated increased food intake in patients after gastrointestinal surgery. This may inform the design of future targeted interventions for this patient group.

Gastrointestinal Nutrient Transit and Enteroendocrine Function After Upper Gastrointestinal Surgery

St. James's Hospital, Ireland

Clinical Research Fellow

Stomach Neoplasms

Stomach Cancer

Glucagon

Infusion of 1% human albumin in normal saline.

Infusion of Exendin 9-39 in 1% human albumin in normal saline

Complete blockade of action of endogenous GLP-1 by Exendin 9-39. Defined as a physiological study, not a clinical trial as such (as advised by the UK MHRA).

Exendin 9-39

Infusion of 1% human albumin in normal saline

Placebo

Geoffrey Roberts, MA BM BCh

Patients who have undergone gastrectomy (removal of the stomach) to treat or prevent cancer are known to have a significantly reduced quality of life. To date, there is very little information on the physiological causes of this. The investigators suspect that overproduction of a hormone (chemical) called glucagon like peptide-1 (GLP-1) released by the lining of the gut may play a role in the reduced appetite, weight loss and low blood sugar symptoms seen in this group. To investigate this, the investigators will study the response of 16 patients who have previously had a gastrectomy to a glucose drink, and a meal, while receiving an infusion of a specific blocker of GLP-1 or placebo. The investigators will examine the levels of sugar and associated hormones in the blood, food consumption and food reward behaviour using standard tools.

Participants will be invited to attend the Clinical Research Facility at Addenbrooke's Hospital for a screening visit, and two whole day study visits. The study has been designed to assess the role of overproduction of GLP-1 by completely blocking its actions, rather than assess the use of the blocking compound as a medication, and is therefore regarded as a physiological study, not a clinical trial.

The goal of this study is to demonstrate the magnitude of effect of GLP-1 on blood sugar and appetite derangement in patients who have had a gastrectomy. This will guide future work on the development of novel treatment paradigms for the post-gastrectomy patient group.

Gastrectomy, Eating Behaviour and GLP-1

The Effect of Glucagon Like Peptide-1 (GLP-1) on Glycaemic Profile and Eating Behaviour Following Gastrectomy

Lowest blood sugar reading during an oral glucose tolerance test while receiving infusion of GLP-1 antagonist. Please note participants will receive infusion of active compound for a maximum of four hours, with no expected effect of compound persisting for more than 30 minutes post-infusion.

60 minute incremental area under the curve (i.e. total) insulin secretion during 50g oral glucose tolerance test while receiving infusion of GLP-1 antagonist. Please note participants will receive infusion of active compound for a maximum of four hours, with no expected effect of compound persisting for more than 30 minutes post-infusion.

As measured by universal eating monitor, total weight of a standardised meal consumed over a measured time in grams per minute.

Will be measured on visual analogue scale and reported as a score out of 100. Higher value indicated more hunger and more satiety.

Food motivation can be measured by response rates to visual cues while being distracted by food related images. Will be measured with and without GLP-1 blockade to investigate effects of GLP-1 on food attention behaviour. Measure is of difference in response time when visual cue is colocated with a food related image vs a non-food related image, indicating degree of bias in attention to food images. Measure is undertaken during infusion at four timepoints - baseline (i.e. fasting), post oral glucose tolerance test (post-OGTT), before a standard meal (pre-meal) and after the meal (post-meal).

Participant motivation to view particular food based cues is assessed by grip strength exerted to maintain those cues. Measure is undertaken during infusion at four timepoints - baseline (i.e. fasting), post oral glucose tolerance test (post-OGTT), before a standard meal (pre-meal) and after the meal (post-meal).

Total consumption amount of a standard meal during study intervention, measured in grams using a universal eating monitor.

Cambridge University Hospitals NHS Foundation Trust

Clinical Research Associate

Infusion of 1% human albumin in normal saline.

Placebo: Infusion of 1% human albumin in normal saline

Infusion of Exendin 9-39 in 1% human albumin in normal saline

Exendin 9-39: Complete blockade of action of endogenous GLP-1 by Exendin 9-39.

Exendin

All participants were randomised to reveal both interventions, so baseline characteristics are reported for the whole study population.

All Participants

Age, Categorical

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

United Kingdom

Region of Enrollment

Mr Geoffrey Roberts

Crossover study - analysis by paired T test

Nadir Blood Glucose

Infusion of Exendin 9-39 in 1% human albumin in normal saline

Exendin 9-39: Complete blockade of action of endogenous GLP-1 by Exendin 9-39. Defined as a physiological study, not a clinical trial as such (as advised by the UK MHRA).

Total Insulin Secretion

Eating Rate During ad Libitum Meal

Unfortunately it proved impossible to collect data on hunger and fullness during the ad libitum meal, due to the cognitive effects of the gastrectomy which all of this group had undergone, meaning participants were unwilling to accurately record these sensations while eating. This data is therefore meaningless and was not analysed.

Decreased Hunger and Satiety Ratings During and After ad Libitum Meal

Time 0

Post OGTT

Pre-meal

Post-meal

Altered Food Attention.

T0 / Baseline

Post-OGTT

Altered Food Motivation

Number of Participants With Infusion Related Adverse Events as Assessed by CTCAE v4

Total Meal Consumption

Infusion of 1% human albumin in normal saline on day one of study. Infusion of Exendin 9-39 in 1% human albumin in normal saline on day two of study (bolus of 7500pmol/kg followed by infusion of 500pmol/kg/minute for 4 hours).

Placebo Then Exendin

Infusion of Exendin 9-39 in 1% human albumin in normal saline on day one of study (bolus of 7500pmol/kg followed by infusion of 500pmol/kg/minute for 4 hours).

Infusion of 1% human albumin in normal saline on day two of study.

Exendin Then Placebo

First Intervention - One Day

Second Intervention - One Day

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study to Allow Access to Pasireotide for Patients Benefiting From Pasireotide Treatment in Novartis-sponsored Studies	NCT01794793	Cushing's Disea... Acromegaly Neuroendocrine ... Pituitary Tumor... Ectopic ACTH Se... Dumping Syndrom... Prostate Cancer Melanoma Negati... Melanoma Negati...	Pasireotide Cabergoline Pasireotide	18 Years -	RECORDATI GROUP
Gastrointestinal Nutrient Transit and Enteroendocrine Function After Upper Gastrointestinal Surgery	NCT03734627	Esophageal Canc... Nutrition Disor... Appetite Disord... Dumping Syndrom... Delayed Gastric... Surgery	Octreotide Acet... Saline Solution Paracetamol Sulfasalazine Duodenal biopsy	18 Years -	St. James's Hospital, Ireland
Gastrectomy, Eating Behaviour and GLP-1	NCT02971631	Gastric Cancer Dumping Syndrom...	Exendin 9-39 Placebo	18 Years - 100 Years	Cambridge University Hospitals NHS Foundation Trust
Study to Allow Access to Pasireotide for Patients Benefiting From Pasireotide Treatment in Novartis-sponsored Studies	NCT01794793	Cushing's Disea... Acromegaly Neuroendocrine ... Pituitary Tumor... Ectopic ACTH Se... Dumping Syndrom... Prostate Cancer Melanoma Negati... Melanoma Negati...	Pasireotide Cabergoline Pasireotide	18 Years -	RECORDATI GROUP

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