Symptoms and General Pathology

All Conditions

Nervous System Diseases

Rare Diseases

Chronic Pain

Cancer Pain

Pain

Neurologic Manifestations

Chronic Graft Versus Host Disease

Adjuvants, Anesthesia

Analgesics

Central Nervous System Depressants

All Drugs and Chemicals

Narcotic Antagonists

Fentanyl

Oxycodone

Morphine

Buprenorphine

Analgesics, Opioid

Narcotics

Anesthetics

Anesthetics, Intravenous

Anesthetics, General

After a titration phase with fast-release oral morphine, once the optimal dosage (no side effects and less than two rescue doses per day) is reached, an equipotent dose of oral sustained-release morphine will be randomly assigned to a patient.

After a titration phase with fast-release oral morphine, once the optimal dosage (no side effects and less than two rescue doses per day) is reached, an equipotent dose of oral extended-release oxycodone will be randomly assigned to a patient.

After a titration phase with fast-release oral morphine, once the optimal dosage (no side effects and less than two rescue doses per day) is reached, an equipotent dosage of transdermal fentanyl will be randomly assigned to a patient.

After a titration phase with fast-release oral morphine, once the optimal dosage (no side effects and less than two rescue doses per day) is reached, an equipotent dosage of transdermal buprenorphine will be randomly assigned to a patient.

Massimo Allegri, MD

Aim of this project is to customize the choice of the strong opioid in the treatment of cancer chronic pain through the identification of patient clinical history and pain characteristics, moreover in the analysis the investigators will also correlate the clinical efficacy and safety of opioid treatment with pharmacokinetic and pharmacogenetic patterns in order to identify variables able to predict the efficacy of the treatment or the patient susceptibility towards a specific treatment.

Furthermore with this study the investigators want to identify the pharmacogenomic characterization responsible for pharmacokinetic variability in the conversion between morphine and other opioids, in order to validate the currently available conversion tables from a pharmacokinetic viewpoint, estimating the influence of the most common genetic polymorphisms, and if this characterization could be useful and cost-effective. This study will also focus on the specific clinical-pharmacological response in the elderly and between male and female and on the interactions between opioids and those anticonvulsant and antidepressant drugs routinely used in the pain therapy (study of pharmacovigilance).

Pain continues to be a major problem in patients with cancer, affecting 25% to 30% of patients with recently diagnosed cancers. The incidence of pain in advanced stages of cancer approaches 70% to 80%. There are a number of reasons that patients with cancer experience chronic pain either related to the disease itself or to its treatment.

Cancer can spread by metastasis or direct invasion, and 90% of patients with metastasis to osseous structures report pain. Patients with cancer can have neuropathic pain due to direct compression of nerves or plexus or spinal cord involvement.

Inadequate treatment and undertreatment are associated with increased pain scores, decreased functional ability, and increased depression and anxiety.

Opioid administration though proven to be effective still meets with resistance from both healthcare operators, who are seldom willing to prescribe these drugs, and patients, who tend to not take them because of many false beliefs still related to opioids.

It is well demonstrated by the literature that opioids are effective in controlling both acute and chronic pain of nociceptive and/or neuropathic origin. Switching type of opioid and/or administration routes (e.g., from oral to neuraxial) is also known to be an important factor in long-term treatment: appropriate conversion tables elucidating drug equipotence and different potency in base of administration route for the different opioids currently available have therefore been devised and validated in the clinical setting.

There have been several attempts to define guidelines for treatment protocols and even recent meta-analyses indicate that morphine should remain the gold standard. However, a general consensus is still lacking, as opioid management depends not only on the type and cause of pain, but also on the patient's history, the pain characteristics and genetic patterns. Which, if any, is the best opioid, in relation with previous characters, to start systemic treatment remains therefore debated. The different effects that different opioids have on spinal cord sensitization as a result of continuous peripheral nociceptive stimulus in long term administration have also been partially investigated.

Current pharmacogenetic publications analyze the pharmacokinetic behavior of opioids in short-term administration, but studies are still lacking on how the pharmacokinetics and analgesic effect vary after repeated administrations of opioids, especially through direct comparison with clinical response. Genetic studies showed differences in the results of opioid treatment related to the variability of the genes that have a role in the pharmacodynamic and pharmacokinetics of opioids. Regardless these studies, the literature has not yet investigated how quantitative and qualitative variability of gene products can influence the efficacy or the toxicity of a specific opioid treatment.

Prospective Study About Clinical and Pharmacogenetic Safety of Opioid Use for Chronic Pain

Chronic Administration of Opioids in Cancer Chronic Pain:an Open Prospective Study on Efficacy, Safety and Pharmacogenetic Factors Influence.

We will define a treatment effective if it will produce a mean reduction of NRS values at least of 40% than basal values. Among all effective treatments, we will identify the best as the one that will have a reduction of NRS to a value of 4 or less in 90% of patients compared to the 70% of the others treatments. To evaluate pharmacological safety the plasma concentrations of the drugs and their metabolites will be measured. We will branch patients population in 3 groups to evaluate the correlation between clinical-pharmacological response and genetics (responder,partially and not responder)

Comparison of plasma levels of opioids and of their metabolites in "responder" patients (clinical effectiveness without side effects), "partially responders" patients (clinical effectiveness without side effects but taking not more than 2 rescue doses per day), and in "non responder" patients (3 groups: clinical un-efficacy, side-effects, tolerance and/or opioid induced hyperalgesia).Evaluation of the correlation between the polymorphisms studied and clinical response; the frequency of allelic variants of interest will be compared in "responder", "partially responder" and "non responder".

University of Pavia

IRCCS Policlinico S. Matteo

Neoplasms

Mouth and Tooth Diseases

Digestive System Diseases

Carcinoma

Carcinoma, Squamous Cell

Headache

Head and Neck Neoplasms

Stomatitis

Mucositis

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastroenteritis

Gastrointestinal Diseases

Mouth Diseases

Stomatognathic Diseases

Tramadol

The main objective of this study is to provide preliminary evidence that FDA approved dose of transdermal buprenorphine in conjunction with oral tramadol can provide adequate analgesia of radiation-induced mucositis pain during treatment and follow up period in head and neck cancer patients.

Transdermal buprenorphine will be started at 5 mcg/hr once a week. Depending on the Visual Analog Scale (VAS) score, it may be increased up to 20 mcg/hr once a week.

Oral tramadol will be started at 50 mg/day. Depending on the Visual Analog Scale (VAS) score, it may be increased up to 400 mg/day.

Each study participant will be issued an Android smartphone, or he or she may use his/her own compatible device (whether or not it has an active data service) to which the OM Pain App will be downloaded and installed. Subjects will receive a preprogrammed alarm four times a day from their smartphones prompting them to directly enter OM pain levels on the device. Patients may submit as many pain entries as they wish beyond the four minimum levels.

Subjects will receive a preprogrammed alarm four times a day from their smartphones prompting them to directly enter OM pain levels on the device. Patients may submit as many pain entries as they wish beyond the four minimum levels.

Oral Mucositis (OM) Pain App

Stuart J. Wong, MD

This is a single-arm prospective clinical trial to determine the safety and feasibility of using transdermal buprenorphine in alleviation of radiation induced mucositis pain in head and neck cancer patients.

Hypothesis: Long-acting transdermal buprenorphine (FDA-approved dose from 5 mcg to 20 mcg /week) in conjunction with oral tramadol (50mg-400mg) as needed for breakthrough pain would lead to significant reduction in mucositis-related pain in locally advanced head and neck cancer patients being treated with radiation therapy by the end of treatment and follow up period of 12 weeks.

This is a single-arm, interventional, supportive care clinical trial for head and neck cancer patients evaluating role of transdermal (TD) buprenorphine and tramadol combination in alleviating radiation-induced mucositis pain. This will generate preliminary data to test the feasibility and efficacy of study drug regimen. The study will also test the clinical usefulness of the smart phone pain app in recording and reporting radiation induced mucositis pain.

Transdermal Buprenorphine for the Treatment of Radiation-Induced Mucositis Pain in Head and Neck Cancer Patients

Transdermal Buprenorphine for the Treatment of Radiation-Induced Mucositis Pain in Head and Neck Cancer Patients: A Pilot Study

The Brief Pain Inventory - Short Form (BPI-sf) is a nine-item self-administered questionnaire used to evaluate the severity of a patient's pain and the impact of this pain on the patient's daily functioning. The patient is asked to rate their worst, least, average, and current pain intensity -- 0 being no pain and 10 being the pain as bad as you can imagine (within the previous 24 hours).

The Oral Mucositis (OM) Pain App is a smartphone application that was designed to permit subjects to key in pain severity using a visual analog 0-10 scale. The amount of pain that a subject feels ranges across a continuum from none (0) to an extreme amount of pain (10). The App is programed with an alarm to prompt the patient to record pain severity at prescribed intervals daily and through spontaneous patient input. Compliance is measured by subjects entering in a value four times a day into the OM Pain App.

Medical College of Wisconsin

Professor

Receiving buprenorphine with short acting full agonist opioid with CPM Rx app to document medication use.

Patients will receive buprenorphine with concurrent FAO \>30 OME and be assessed for withdrawal, pain, and other symptoms.

Use of buprenorphine with FAO > 30 OME

The CPM Rx application is used on smart phones to allow patients to input time-stamped data about medication type, dosage, and pain score. This will allow analysis of trends in self-reported pain and optimal dosing patterns. Usage over three months will be assessed.

CPM Rx application use

Marcin Chwistek, MD

Dylan Sherry, MD

This study will evaluate patients on both buprenorphine and full agonist opioids (FAO) to assess for withdrawal symptoms. Patients will be evaluated by clinicians and using validated tools to assess for pain and withdrawal. At the same time, patients will use a CPM Rx application on their phone to track medication use.

This prospective study will recruit patients with pain related to cancer or its treatment who are on buprenorphine in combination with a full agonist opioid where dose of the full agonist opioids (FAO) is \> 30 mg OME per day. They will be provided a mobile application (CPM Rx) for reporting of pain level daily and at each as needed dose. Withdrawal will be assessed using a modified Clinical Opioid Withdrawal Scale (COWS) score and patients will be instructed to be aware of changes in these symptoms. They will also be followed in person at the initial visit, and at days 14, 28, 56 , and 84 with Brief Pain Inventory (BPI) and COWS scale to assess for pain or withdrawal and other reported side effects. Pill counts will be done on days 28, 56, and 84 to further assess medication usage. Nurses will check-in to complete BPI and ask about withdrawal symptoms at days 42 and 70. The study seeks to assess if patients on buprenorphine and FAO have withdrawal symptoms, what are the highest doses of buprenorphine and FAO tolerated, and assess usage of the CPM Rx app. Each patient will be followed on the study for 3 months, unless the choose or it is deemed appropriate to end sooner.

Buprenorphine for Cancer Pain

Effective Use of Buprenorphine for Long-Acting Pain Relief in Combination With Short-Acting Full Agonist Opioids for Cancer Related Pain

Patients will be assessed on days 0 (baseline), 14, 28, 42, 56, 70, and 84 to assess for withdrawal using the validated COWS tool in conjunction with clinical assessment.

Doses of buprenorphine and FAO will be assessed on days 0 (baseline), 14, 28, 42, 56, 70, and 84 with maximum dose of FAO and associated does of buprenorphine and maximum dose of buprenorphine and associated dose of FAO determined at the end of the study.

Usage of the app will be monitored and described at the end of the study

Fox Chase Cancer Center

Director of Supportive Oncology and Palliative Care Program

Oscar Corli, MD

Pain, in neoplastic disease, is a symptom with severe negative impact on the quality of life of patients and a high incidence, with values around 70-90% in advanced and metastatic stages. Than 20 years the main reference for the pharmacological treatment of cancer pain are the guidelines produced by the World Health Organization (WHO). This document shows that the use of opioid drugs is the mainstay of treatment, with particular reference to opioids "major" (3 rd step of the analgesic ladder). The 4 opioids more most commonly prescribed in Italy (oral morphine and oxycodone, fentanyl and buprenorphine transdermal), based on the data currently available, have an analgesic effect would partly overlap but with different percentages of non-responders (NR), a different need to increase the dose over time to maintain adequate analgesia, a different action to the switch to another molecule for ineffectiveness analgesic. The observations described suggest that opioids, although they belong to the same family drug may not be fully comparable with regard to the clinical effects products. Important differences are known on the pharmacokinetic and pharmacodynamic and, more recently, also in terms of pharmacogenomics. This is a comparative study of analgesic strategies based on the use of the 4 mentioned opioids, going to look for possible differences in terms of analgesic efficacy, changes in dose over time, use of switch or permanent abandonment of treatment, parallel to the contour of the side effects. The associated sub-project will link the structure gene of patients and clinical results have emerged.

RCT Comparing the Analgesic Efficacy of 4 Therapeutic Strategies Based on 4 Different Major Opioids (Fentanyl, Oxycodone, Buprenorphine vs Morphine) in Cancer Patients With Moderate/Severe Pain, at the Moment of Starting 3rd Step of WHO Analgesic Ladder.

The proportion of subjects with an increase of opioid daily dose \> 5% compared with the basal dosage (OEI%).

Evaluation of the proportion of Non-Responder (NR) participants. NR correspond to the subjects who do not report any analgesic effects, with a P.I.D. (pain intensity difference) from visit 6 and visit 1 =/\< 0%, (using a 0-10 NRS ). It includes the situations of average pain intensity "stable" or "worsened" at day 28 compared with baseline values.

Evaluation of the proportion of subjects who report full analgesia (full responders: FR). FR is operationally defined as a patient with a P.I.D. =/\> 30% from visit 6 and visit 1 (NRS 0 to 10).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Prospective Study About Clinical and Pharmacogenetic Safety of Opioid Use for Chronic Pain	NCT00916890	Chronic Pain	Morphine Oxycodone Fentanyl Buprenorphine	18 Years -	IRCCS Policlinico S. Matteo
Transdermal Buprenorphine for the Treatment of Radiation-Induced Mucositis Pain in Head and Neck Cancer Patients	NCT04752384	Head and Neck S...	Buprenorphine Tramadol Oral Mucositis ...	18 Years - 80 Years	Medical College of Wisconsin
Buprenorphine for Cancer Pain	NCT05910190	Cancer-Related ...	Use of buprenor... CPM Rx applicat...	18 Years -	Fox Chase Cancer Center
Buprenorphine for Cancer Pain	NCT05910190	Cancer-Related ...	Use of buprenor... CPM Rx applicat...	18 Years -	Fox Chase Cancer Center
Transdermal Buprenorphine for the Treatment of Radiation-Induced Mucositis Pain in Head and Neck Cancer Patients	NCT04752384	Head and Neck S...	Buprenorphine Tramadol Oral Mucositis ...	18 Years - 80 Years	Medical College of Wisconsin
RCT Comparing the Analgesic Efficacy of 4 Therapeutic Strategies Based on 4 Different Major Opioids (Fentanyl, Oxycodone, Buprenorphine vs Morphine) in Cancer Patients With Moderate/Severe Pain, at the Moment of Starting 3rd Step of WHO Analgesic Ladder.	NCT01809106	Cancer Cancer Pain	Morphine Fentanyl Buprenorphine Oxycodone	18 Years -	Mario Negri Institute for Pharmacological Research
Prospective Study About Clinical and Pharmacogenetic Safety of Opioid Use for Chronic Pain	NCT00916890	Chronic Pain	Morphine Oxycodone Fentanyl Buprenorphine	18 Years -	IRCCS Policlinico S. Matteo
RCT Comparing the Analgesic Efficacy of 4 Therapeutic Strategies Based on 4 Different Major Opioids (Fentanyl, Oxycodone, Buprenorphine vs Morphine) in Cancer Patients With Moderate/Severe Pain, at the Moment of Starting 3rd Step of WHO Analgesic Ladder.	NCT01809106	Cancer Cancer Pain	Morphine Fentanyl Buprenorphine Oxycodone	18 Years -	Mario Negri Institute for Pharmacological Research

Spots Global Cancer Trial Database for buprenorphine