Gland and Hormone Related Diseases

All Conditions

Diseases and Abnormalities at or Before Birth

Nervous System Diseases

Neoplasms

Thyroid Diseases

Congenital Abnormalities

Pituitary Diseases

Hypothyroidism

Pituitary Neoplasms

Endocrine System Diseases

Hypothalamic Diseases

Brain Diseases

Central Nervous System Diseases

All Drugs and Chemicals

Hormones

Thyrotropin-Releasing Hormone

Hormone Antagonists

Subjects receiving TRH (Thyrotropin Releasing Hormone)

TRH (Thyrotropin Releasing Hormone)

Joanna Klubo-Gwiezdzinska, M.D.

This study will determine the safety and activity of a new formulation of thyrotropin-releasing hormone (TRH), a drug used for diagnosing and evaluating patients with certain thyroid gland abnormalities. Normal thyroid gland function depends on proper chemical signaling between the thyroid gland, the hypothalamus (the part of the brain where TRH is made), and the pituitary (another part of the brain). The TRH test helps assess this interaction. Production of the only FDA-approved preparation of TRH was stopped in July 2002. As a result, to have a continuous source of TRH available for NIH clinical and research purposes, the NIH Clinical Center (CC) Pharmacy Department produced a pharmaceutical grade formulation of TRH for patient use. This study will test the CC formulation in healthy volunteers to show that its activity and side effects are similar to those of the previously available commercial test preparation. It will then be studied in CC patients for whom the diagnostic test is recommended.

Healthy volunteers between 18 and 65 years of age and all patients requiring TRH evaluation of hypothalamic-pituitary-thyroid gland interaction may be eligible for this study. Patients include those with pituitary reserve, inconsistent thyroid function test, inappropriate TSH secretion, or pre- and post-operative evaluation of pituitary tumors. Normal volunteers will be screened with a medical history, physical examination, and blood tests. Women of child-bearing potential will be given a pregnancy test; pregnant and breast-feeding women may not participate.

The TRH test procedure will be the same for healthy volunteers and patients. All participants fast from midnight before the morning of the test. In the morning, a catheter (flexible plastic tube) is inserted into an arm vein for easy injection of the TRH and collection of blood samples. Blood pressure is monitored before and during the test. A blood sample is drawn, and then TRH is given through the catheter over a 1-minute period. Another nine blood samples are collected over a 3-hour period from the time of the TRH injection for measuring levels of various hormones. A total of less than 4 tablespoons of blood is taken for the test.

Thyrotropin releasing hormone (TRH) is a neuropeptide used in the diagnostic evaluation of patients with dysfunction of the hypothalamic-pituitary-thyroid (HPT) axis. In healthy individuals, administration of TRH intravenously results in pituitary secretion of thyrotropin \[thyroid-stimulating hormone (TSH)\], which in turn stimulates the thyroid gland release of thyroid hormones; thyroxine (T4) and triiodothyronine (T3). TRH stimulates the secretion of other pituitary hormones under normal physiologic as well as pathologic conditions.

Under this protocol, TRH is used for routine diagnostic testing and research studies in adults and children. It is produced by the Pharmaceutical Development Section of the Clinical Center Pharmacy at the NIH. The safety, activity and comparability of this preparation were demonstrated in a small group of normal volunteers prior to its release for diagnostic and research use.

Study of Thyrotropin-Releasing Hormone in Normal Volunteers and in Patients With Thyroid or Pituitary Abnormalities

Study of Thyrotropin Releasing Hormone in Patients With Thyroid or Pituitary Abnormalities

Serum TSH Levels in Response to TRH Administration

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

Thyrotropin Releasing Hormone

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

This study was conducted under an IND because the TRH was produced at NIH after the FDA approved manufacturer stopped producing the product. The intent of the study was to provide TRH for diagnostic purposes for patients at the NIH.

Dr Joanna Klubo-Gwiezdzinska

2 participants did not have results drawn at 180 minutes

TSH Response to TRH

Overall Study

Nutritional and Metabolic Diseases

Behaviors and Mental Disorders

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Symptoms and General Pathology

Musculoskeletal Diseases

Digestive System Diseases

Heart and Blood Diseases

Immune System Diseases

Skin and Connective Tissue Diseases

Infections

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Rare Diseases

Diabetes Mellitus

Anxiety Disorders

Depressive Disorder

Dementia

Kidney Diseases

Alzheimer Disease

Lung Diseases, Obstructive

Pulmonary Disease, Chronic Obstructive

Osteoporosis

Hyperlipoproteinemias

Hyperlipidemias

Crohn Disease

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Colitis, Ulcerative

Ulcer

Depression

Heart Failure

Asthma

Stroke

Hypertension

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Hepatitis A

Hepatitis

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Hepatitis, Chronic

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Bronchitis, Chronic

Diverticulum

Diverticular Diseases

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Female Urogenital Diseases and Pregnancy Complications

Male Urogenital Diseases

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Chronic Disease

Disease Attributes

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Bone Diseases, Metabolic

Metabolic Diseases

Esophageal Motility Disorders

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Deglutition Disorders

Esophageal Diseases

Dyslipidemias

Lipid Metabolism Disorders

Muscular Diseases

Neurologic Manifestations

Communicable Diseases

Respiratory Tract Infections

Bronchial Diseases

Brain Ischemia

Cerebrovascular Disorders

Pathological Conditions, Anatomical

Familial Alzheimer Disease

Chronic Graft Versus Host Disease

Intervention group (n = 163) Intervention: Participates in DIMAC02 Program

Health Administrative Data Group (n = 1630) Number of matched data controls. Not taking part in intervention.

Integrated Approach For Chronic Diseases (DIMAC02) is an integrated approach for chronic disease prevention and management services that aims to improve and coordinate different regional initiatives in 11 Family Medicine Groups(FMG) related to : Self-management, Case management, Patient-centred care for persons with multimorbidity, Motivational approach, Interprofessional collaboration. DIMAC 02 specific objectives are: 1) To make available, in FMG's, an interdisciplinary educational intervention for prevention and management of chronic diseases for patients with low and high risk for complication. 2) To Increase the flow of communications between FMG and hospital facilities to improve continuity of care.

DIMAC02

Martin Fortin, MD, M.Sc

The aim of Patient-Centred Innovations for Persons With Multimorbidity (PACE in MM) study is to reorient the health care system from a single disease focus to a multimorbidity focus; centre on not only disease but also the patient in context; and realign the health care system from separate silos to coordinated collaborations in care. PACE in MM will propose multifaceted innovations in Chronic Disease Prevention and Management (CDPM) that will be grounded in current realities (i.e. Chronic Care Models including Self-Management Programs), that are linked to Primary Care (PC) reform efforts. The study will build on this firm foundation, will design and test promising innovations and will achieve transformation by creating structures to sustain relationships among researchers, decision-makers, practitioners, and patients. The Team will conduct inter-jurisdictional comparisons and is mainly a Quebec (QC) - Ontario (ON) collaboration with participation from 3 other provinces: British Columbia (BC); Manitoba (MB); and Nova Scotia (NS). The Team's objectives are: 1) to identify factors responsible for success or failure of current CDPM programs linked to the PC reform, by conducting a realist synthesis of their quantitative and qualitative evaluations; 2) to transform consenting CDPM programs identified in Objective 1, by aligning them to promising interventions on patient-centred care for multimorbidity patients, and to test these new innovations' in at least two jurisdictions and compare among jurisdictions; and 3) to foster the scaling-up of innovations informed by Objective 1 and tested/proven in Objective 2, and to conduct research on different approaches to scaling-up. This registration for Clinical Trials only pertains to Objective 2 of the study.

A recent systematic review on the prevalence of Multimorbidity (MM) recommended a count of 3+ chronic diseases, with no focus on any single chronic disease in particular. This definition identifies a more vulnerable population with higher needs, lower income or poverty, poorer outcomes and challenging processes of care. It includes people with a wide array of complexity from the uncomplicated course of minimally interacting chronic diseases to the highly complex MM patients. MM is not only important due to the burden on patients, but because it accounts for high utilization. The definition represents a continuum of vulnerability in which there are many opportunities for prevention and management. Despite the high prevalence of MM, most research and health care is still based on a single disease paradigm which may not be appropriate as 45% of primary care patients have MM. A recent Cochrane systematic review on the impact of interventions for patients with MM has identified a paucity of studies internationally with mixed results, thus paving the way for the work of this Team. The most promising intervention, to date, was enhanced teamwork in a multifaceted intervention involving multiple professionals.

Patient-Centred Partnerships between Patients and Providers: The definition of patient-centred partnerships is derived from Canadian policy reports: "collaboration between informed, respected patients and a healthcare team." There is an internationally accepted comprehensive operational definition with four components which will guide many aspects of the proposed research program: first, exploring the patients' diseases and the illness experience; second, understanding the whole person in context; third, finding common ground; and fourth, enhancing the patient-provider relationship. There is empirical evidence for the impact of patient-centred partnerships on better patient outcomes and lower costs. Systematic reviews of interventions indicated promising results for feasible practice-based interventions targeting both providers and patients.

Canadian policy reports defined this second facet of patient-centredness, as "seamless coordination and integration of care." Transitions requiring coordination are a key feature of care for patients with MM. Coordination has been shown to positively impact: symptom relief; social functioning; hospital re-admission and related costs. Papers reviewed by this Team identified the most promising type of intervention to be structured delivery system re-design.

STUDY #2.1 Qualitative Evaluation of the aligned Programs Purpose: The study will: assess how the transformed program performs; distinguish between components of the interventions; and identify contextual factors that may have influenced the content and effectiveness of the intervention. It will also examine the local barriers and facilitators as well as the transitions and coordination of care.

Methods and design: The Team will conduct a qualitative evaluation of the transformed programs to explain how various contexts influence observed effects \[1\] including the context of the health care systems in each province. A recent example of this research approach in Canada is Best et al, 2012 \[2\]. Data will be obtained from interviews and written documents. In-depth interviews will be conducted among the four categories of stakeholders. This will include: a) decision-makers (n = 10); b) primary care physicians (n = 10); c) professionals doing the interventions (n = 10); and a d) purposive sample of patients with multimorbidity (n = 10) and their informal caregivers (n=10) \[51\]. The number of interviews are estimates and will be guided by the saturation of data \[3\].

Data collection: In-depth interviews, lasting 30 to 60 minutes will ensure complete and detailed participation. The data collection will be held during the second year of the transformed program. The interview guides will examine how the context variables influence the effects and the elements that could potentially inform the development of future interventions. All interviews will be audiotaped and transcribed verbatim. Additionally, written documents will be collected (program team meeting summaries, a sample of 10 medical records or research records at each participating site, a checklist describing the fidelity of the intervention, all documents produced specifically for the intervention) to provide an in-depth understanding of the various contexts in which the interventions occurred.

Data analysis: The data will be analyzed using an iterative and interpretative approach \[4\]. The data from all participants will be examined through both independent and team analysis occurring in a concurrent manner to build and develop on the emerging themes. A coding template will be developed and edited as new themes emerge while others are reclassified or discarded. A data management software will be used to organize the coded data and identify exemplar quotes reflecting the central themes. All written documents will undergo a content analysis. The final step of the analysis will be the triangulation of the synthesis of the themes from the stakeholder participants and the content analysis of the documents.\[3-4\] STUDY #2.2: Evaluation of effects of the aligned Programs Setting: The same consenting participating sites as described in study 2.1. The methods presented below are for one setting and will be duplicated in the second setting. Patients are referred to receive the services of these programs by their providers. The intervention the investigators are testing here is the aligned programs. Patients referred to these programs are new patients and have never been exposed to the intervention. In addition to the main reason for referral to the program, the referral form will also include eligibility details for the evaluation, including diagnoses.

Patient sample: Patients recruited for the study will be cognitively intact and literate and aged between 18 and 80 years of age. The upper limit of 80 years is to avoid recruiting patients at risk of being institutionalized or dependent during the follow-up. Patients will present at least three chronic conditions.

Methods and Design: Patients agreeing to participate will complete questionnaires at baseline (T1) collecting the sociodemographic data and baseline measures, which will be used to document equivalence between groups (groups are defined below). Effectiveness of the aligned program will be assessed using three strategies.

1. To measure short-term effects (4 months), a randomized controlled trial (RCT) design with a delayed intervention will be used \[5\]. Eligible patients will be randomized after consent to receive either the intervention within a short period of time (Group A) or 4 months later (Group B); self-reported mailed questionnaires will be completed at baseline (T1) for all patient participants, 4 months after the end of the intervention for group A (T2) and 4 months after baseline for control group B (T2). This will constitute the short-term measure of effectiveness of the intervention. Group B will then receive the intervention.
2. To measure the mid-term effects (one year) on patient-reported outcomes, a before and after study is proposed combining groups A and B together. The patients will complete the same questionnaire 12 months after the end of the intervention (T3).
3. To measure mid-term (T3) and long-term effects (T4 after 2 years) on health services utilization and cost, all patients (groups A and B) will provide consent to give access to their health administrative (HA) data. At baseline, a control Group C will be constituted using anonymized HA data. Patients will be matched for gender, age, region and main three diagnoses. The Team will build algorithms for matching every set of controls. Groups A and B together will be compared to this propensity matched control group C in a before-after study using administrative (HA) data.

Variables and outcome measures: The variables fall into 5 categories: sociodemographic; PC context; main co-variables of interest; primary outcomes; secondary outcomes. Socio-demographic characteristics include gender, age, education, family income, marital status, occupation, housing and number of persons living under the same roof. Context variables refer to type of PC organization in which the intervention occurs (Family Medicine Group). The three main co-variables of interest are the Team's three innovations: self-reported multimorbidity (measured by the Disease Burden Morbidity Assessment \[6\]; patient-centred partnership (Patient Perception of Patient-Centredness Scale \[7-9\]); and Patient centered coordination (the Patient Perceptions of Transitions in care, adapted by the investigators from Coleman \[10\]). The two primary outcome measures are the Health Education Impact Questionnaire (HeiQ) that provides a broad profile of the potential impacts of patient education interventions \[11\] and the level of perceived disease-management self-efficacy using the 6-item Self-Efficacy for Managing Chronic Disease (SEM-CD) \[12\]. Secondary patient perceived outcomes will be the VR-12 as a measure of health status and the "EuroQoL group" instrument called "EQ5D" as a measure of Quality of Life \[13\]. The Kessler psychological distress scale K-6 will measure psychological distress \[14\]. The investigators will also use a questionnaire on health behaviors \[15\]. Finally, HA data will also be used as secondary outcomes to compare health care utilization and cost before and after the intervention. HA data will include emergency department visits, avoidable hospital admissions, readmissions, time to first primary care visit after emergency department visit and continuity of care.

Data analysis: Investigators will first describe participants' baseline characteristics in each group and compare among groups. To evaluate short-term effect, Groups A and B will be compared on T2 scores with an analysis of co-variance (ANCOVA) adjusted for T1 scores \[16\]. To document mid-term effects, a before and after measures analysis of variance will be used to study the evolution of continuous variables collected 3 times \[17\]. Sub-analyses by gender will be performed. Health system costs in intervention and control groups will be evaluated by using amounts paid to providers based on provincial fee schedules and cost-weighted utilization of institutions including hospitals and long-term care. Utilization records obtained from HA data will be multiplied by applicable cost weights \[18\] The methods employed will model the individual patient-level costs incurred in the health system, using methods developed for costing using administrative data\[19\]. Incremental resources in the intervention group will be identified and costed using applicable time/resource inputs and relevant wage rates following guidelines for economic evaluation in health interventions \[20\].

Patient-Centred Innovations for Persons With Multimorbidity - Quebec

Health Education Impact Questionnaire (HeiQ). Score: Reliable improvement

Multimorbidity/Chronic Disease (MM-21): Score: number of Chronic diseases

Health Status (VR-12): Score: Physical Component Summary (PCS) and the Mental Component Summary (MCS)

Psychological Well-being (Kessler 6 Scale).Score: mean

Lifestyle/Health Behaviours Questionnaire. Score: mean

Patient Perception of Transitions of Care. Score: Mean

Self-Efficacy for Managing Chronic Disease Scale (SEM-CD). Score: mean

Patient Perception of Patient-Centredness (PPPC). Score: Mean

Canadian Institutes of Health Research (CIHR)

Western University, Canada

Agence de la Sante et des Services Sociaux du Saguenay-Lac-Saint-Jean

Université de Sherbrooke

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of Thyrotropin-Releasing Hormone in Normal Volunteers and in Patients With Thyroid or Pituitary Abnormalities	NCT00054756	Healthy Pituitary Disea... Thyroid Disease	TRH (Thyrotropi...	2 Years -	National Institutes of Health Clinical Center (CC)
Patient-Centred Innovations for Persons With Multimorbidity - Quebec	NCT02789800	Hypertension Depression Anxiety Musculoskeletal... Arthritis Rheumatoid Arth... Osteoporosis Chronic Obstruc... Asthma Chronic Bronchi... Cardiovascular ... Heart Failure Stroke Transient Ische... Ulcer Gastroesophagea... Irritable Bowel Crohn's Disease Ulcerative Coli... Diverticulosis Chronic Hepatit... Diabetes Thyroid Disorde... Cancer Kidney Disease Urinary Tract P... Dementia Alzheimer's Dis... Hyperlipidemia HIV	DIMAC02	18 Years - 80 Years	Université de Sherbrooke

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