Change in Quality of Life After Addition of Weekly 40 mg Pegvisomant/Placebo in Controlled Acromegalic Patients

Learn more about:
Related Clinical Trial
The TMS Treatment for Postoperative Headache in GH Tumor A Pilot Study of Empagliflozin in the Treatment of Acromegalic Cardiomyopathy A Study to Assess the Safety, Tolerability, and Efficacy of IONIS-GHR-LRx Administered in Patients With Acromegaly Rhinological Outcomes in Endonasal Pituitary Surgery Co-treatment With Pegvisomant and a Somatostatin Analogue (SA) in SA-responsive Acromegalic Patients Study to Allow Access to Pasireotide for Patients Benefiting From Pasireotide Treatment in Novartis-sponsored Studies A Four-Part Study to Assess the Safety, Tolerability, PK and PD of ONO-5788 in Healthy Adult Volunteers The Effect of Subcutaneous Infusions of 3 Doses of DG3173 on Growth Hormone Levels in Untreated Acromegalics One Year Follow-up of Study 2-79-52030-207 (PRIMARYS) in Acromegalic Patients With Macroadenoma Study in Polish Acromegalic Patients Treated With Somatuline Autogel Long Term Use of Somavert (Pegvisomant) For A Regulatory Post Marketing Commitment Plan Predictive Factors of Response to Somatostatin Analogues in Acromegalic Patients With Persistent Disease Following Surgery The Observational Study of Growth Hormone-secreting Pituitary Tumors Change in Quality of Life After Addition of Weekly 40 mg Pegvisomant/Placebo in Controlled Acromegalic Patients Study to Evaluate the Efficacy and Safety of Sandostatin LAR at High Dose or in Combination Either With GH-receptor Antagonist or Dopamine-agonist in Acromegalic Patients Efficacy and Safety of Lanreotide Autogel (60, 90 or 120 mg) in Acromegalic Patients Substrate Metabolism and Insulin Sensitivity in Acromegalic Patients Before and After Treatment Single-dose Study to Evaluate the Absolute Bioavailability and Mass Balance of ONO-5788 Study Comparing SOM230 Subcutaneously and Sandostatin Subcutaneously in Acromegalic Patients Therapeutic Strategies in Acromegalic Subjects Treated With Lanreotide 120mg Preoperative Lanreotide Treatment in Acromegalic Patients With Macroadenomas Study to Assess the Efficacy of an Extended Injection Interval Schedule of Lanreotide Autogel in Acromegalic Subjects Phase II Study With ITF2984 in Acromegalic Patients Non Interventional Study For Patients Treated With Somavert® Single Dose Pharmacology Study of DG3173 and Octreotide in Acromegalic Patients. Estrogen Treatment in Acromegalic Women Pharmacodynamics Of Product Octreotide Acetate Lar 30 Mg, Imported And Distributed By The Laboratory Chemical Pharmaceutical Bergamo Ltda., Compared To Product Sandostatin LAR ® (Octreotide Acetate LAR) 30 MG Manufactured By Novartis Biosciences S / A. ACRODAT Prospective Evaluation Study Pegvisomant And Sandostatin LAR Combination Study Lanreotide as Primary Treatment for Acromegalic Patients With Pituitary Gland Macroadenoma Open Label Extension Study Evaluating Safety and Biological Activity of C2L-OCT-01 PR in Acromegalic Patients Efficacy and Safety of C2L-OCT-01 PR in Acromegalic Patients Efficacy of Octreotide Acetate and Cabergoline in Patients With Acromegaly Canadian Pegvisomant Compassionate Study In Acromegalic Patients Efficacy and Safety Study of Varying Doses of Lanreotide Autogel in Patients With Acromegaly Hormonal Outcomes in Acromegalic Patients With Treated Surgery With or Without Long Acting Somatostatin Analogues Tissue Biomarker for Pegvisomant Action Sandostatin LAR Depot vs. Surgery for Treating Acromegaly Safety and Efficacy of Octreotide Long Acting Release (LAR) in Treatment Naïve Acromegalic Patients Lanreotide Autogel 120 mg at Extended Dosing Intervals (>4 Weeks) in Acromegalic Subjects Comparable Effects of Lanreotide Autogel and Octreotide LAR on GH, IGF-I Levels and Patient Satisfaction Predictive Factors Study Sleep Apnea Syndrome on Acromegaly: Impact of the Treatment on the Carbohydrates Metabolism. Growth Hormone Feedback to Insulin-like Growth Factor-I (IGF-1) and Oral Glucose Tolerance Test (OGTT) Somatostatin Analog Treatment of Acromegaly Before Pituitary Surgery : Comparison With Neurosurgery Alone Effect of 120mg Somatuline Autogel at Different Dose Intervals (28, 42 or 56 Days) in Patients With Acromegaly Acromegaly – Before and After Treatment Study to Assess the Efficacy and Safety of Repeated Administration of BIM 23A760 in Patients With Acromegaly Measurement of Outcome of Surgical Treatment in Patients With Acromegaly Non Interventional Post Marketing Programme in Acromegaly Short and Long Term Efficacy of Combined Cabergoline and Octreotide Treatment in Acromegalic Patients Cardiovascular Outcome After Surgery or Somatostatin Analogues Efficacy/Safety of Octreotide Acetate in Patients With Uncontrolled Acromegaly Study Assessing the Efficacy and Safety of Octreotide Acetate in Patients With Acromegaly, With Micro or Macroadenomas Long Term Study With B2036-PEG Octreotide Efficacy and Safety in First-line Acromegalic Patients Long-term Safety and Efficacy Study of Octreotide Implant in Patients With Acromegaly An Extension Study to Assess the Long-term Safety and Efficacy of Pasireotide in Patients With Acromegaly Study of the Effect of Growth Hormone-Releasing Hormone Antagonist on Growth Hormone Release in Acromegaly Clomiphene Citrate for Treatment of Acromegaly Cardiac (CMRI) Assessment of Acromegaly Acromegaly Combination Treatment Study Efficacy and Safety of Octreotide Capsules (MYCAPSSA) in Acromegaly Assessment of Changes in Metabolic Activity in Liver & Skeletal Muscle in Patients Suffering From Acromegaly Changes of Left Ventricular Mass and Cardiac Function in Patients With Active Acromegaly During Treatment With the Growth Hormone Receptor Antagonist Pegvisomant Assessment of BIM23B065, Given as Repeated Subcutaneous Injection in Subjects With Acromegaly A Study to Evaluate the Risk of Developing a Heart Condition Called Valvular Regurgitation in Patients With Acromegaly Treated With Either Lanreotide or Octreotide Pasireotide LAR and Pegvisomant Study in Acromegaly Effects of Sandostatin LAR® in Acromegaly Open Label Study of Octreotide Implant in Patients With Acromegaly Efficacy and Safety Study of Octreotide Implant in Patients With Acromegaly Somatuline Autogel: Acromegaly Self/Partner Injection Study A Study To Compare The Efficacy And Safety Of Pegvisomant To That Of Sandostatin Lar Depot In Patients With Acromegaly Efficacy and Tolerability of Lanreotide (Autogel 120 mg) in Patients With Acromegaly Study to Predict Lanreotide-induced Disease Activity Normalization in Acromegaly Impact of Somatostatin Analogs vs. Surgery on Glucose Metabolism in Acromegaly Prospective Study on Changes in Acromegaly Study to Determine the Maximum Tolerated Dose, Safety and Tolerability of a Single Dose of Lanreotide Prolonged Release Formulation (PRF) in Subjects With Acromegaly Dose Escalation of Octreotide-LAR as First-Line Therapy in Resistant Acromegaly Assessment of the Ability of Subjects With Acromegaly or Their Partners to Administer Somatuline Autogel Efficacy and Safety of Lanreotide Autogel® 60, 90 or 120 mg With Lanreotide 40 mg Prolonged Release (PR) in Acromegaly An Open-label, Multi-center, Expanded Treatment Protocol of Pasireotide LAR in Patients With Acromegaly Assessment of Airway in Patients With Acromegaly for Predicting Successful Tracheal Intubation Quality of Life (QoL) in Subjects With Acromegaly Under Lanreotide Autogel® Treatment. A Study to Evaluate the Long-Term Safety and Efficacy of Paltusotine for the Treatment of Acromegaly (ACROBAT Advance) An Study to Evaluate the Safety and Efficacy of Paltusotine for the Treatment of Acromegaly (ACROBAT Edge) Study to Evaluate Patients With Acromegaly Treated With Lanreotide Autogel (Somatuline ATG) IGF-I and Free Fatty Acids Isn Glucose Metabolism in Acromegaly Safety and Efficacy of Pasireotide Long Acting Release (LAR) vs. Octreotide LAR in Patients With Active Acromegaly Study of Management of Pasireotide-induced Hyperglycemia in Adult Patients With Cushing’s Disease or Acromegaly Growth Hormone, IGF-1 and Medical Treatment in Acromegaly: Are There Effects on Gut Hormone Physiology and Postprandial Substrate Metabolism? Efficacy and Safety of Pasireotide Long Acting Release (LAR) Versus Octreotide LAR or Lanreotide Autogel (ATG) in Patients With Inadequately Controlled Acromegaly Rehabilitation Program in Patients With Acromegaly Acute Application of Pegvisomant and Octreotide in Acromegaly Lanreotide Autogel-120 mg as First-Line Treatment of Acromegaly Prediction of Tumor Shrinkage in Acromegaly Somatostatin Analogue Treatment of Acromegaly: Molecular Aspects Safety and Efficacy of Long-acting Repeatable Octreotide Acetate for Injectable Suspension vs. Surgery in Treatment-naïve Patients With Acromegaly SAGIT for Classification of Patients With Acromegaly in Clinical Practice Lanreotide Autogel in Patients With Acromegaly Previously Treated With Octreotide LAR Olfactory Function and Olfactory Bulb Volume in Acromegaly Patients Late Effects of Radiosurgery on Acromegaly Study Ultrasound Guided Octreotide LAR Injection in Acromegaly Comparison of Oral Octreotide Capsules to Injectable Somatostatin Analogs in Acromegaly A Trial to Assess the Long-term Safety of Octreotide Subcutaneous Depot in Patients With Acromegaly Safety, Tolerability, and Efficacy of IONIS-GHR-LRx in Patients With Acromegaly Being Treated With Long-acting Somatostatin Receptor Ligands A Trial to Assess Efficacy and Safety of Octreotide Subcutaneous Depot in Patients With Acromegaly Strict IGF-1 Control in Acromegaly Extension Study of IONIS-GHR-LRx Administered to Participants With Acromegaly Being Treated With Long-acting Somatostatin Receptor Ligands Treatment of Acromegaly With Somatostatin Analogs: GH vs. IGF-I as Primary Biochemical Target Fractionated Stereotactic Radiotherapy in Patients With Acromegaly Validation Study of the SAGIT® Instrument in Acromegaly Developing a Simple Recognition System of Acromegaly Glucose Tolerance in Acromegaly: The Influence of GH-excess on Glucose Metabolism and Insulin Resistance Surgical Versus Medical Treatment of Acromegaly A Study to Evaluate the Safety and Efficacy of Paltusotine for the Treatment of Acromegaly (ACROBAT Evolve) Acromegaly & Sleep Apnoea Somatuline Predictive Factors in Acromegaly and NET Acromegaly Treatment Quality of Life Study Lanreotide Levels in Acromegaly Description of Sign-and-symptom Associations at Acromegaly Diagnosis. Treatment Patterns and Treatment Outcomes for Acromegaly Ectopic Lipid Deposition and Insulin Resistance in After Treatment of Acromegaly Physiopathology of Sodium Retention in Acromegaly Somatuline® Depot (Lanreotide) for Acromegaly Post-Marketing Observational Study Peri- and Post-operative Dynamics of the Growth Hormone Axis in Subjects With Acromegaly During the First Year After Surgical Resection The Longitudinal Approach to Acromegaly: A Pattern of Treatment and Comparative Effectiveness Research Preoperative Octreotide Treatment of Acromegaly The Treatment and Natural History of Acromegaly Bone MicroArchitecture in Acromegaly Reproducibility and Utility of OGTT in Acromegaly A Prospective Study of Outcome After Therapy for Acromegaly Epidemiology of Acromegaly in Denmark 1991-2010 Programme of Acromegaly Screening in Patients With Associated Somatic Disorders Acromegaly: Patient And Physician Perspectives

Brief Title

Change in Quality of Life After Addition of Weekly 40 mg Pegvisomant/Placebo in Controlled Acromegalic Patients

Official Title

The Effects of Weekly Administration of 40 mg Pegvisomant or Placebo on Quality of Life and Insulin Sensitivity in Acromegalic Patients With Normal IGF-I Concentrations During Long-Term Treatment With Long-Acting Somatostatin Analogs

Brief Summary

      Study Synopsis Study Title: Double blind, single centre, cross-over study on the effects of
      weekly subcutaneous administration of 40 mg pegvisomant or placebo on quality of life and
      insulin sensitivity in acromegalic patients with normal serum IGF-I concentrations during
      long-term treatment with long-acting somatostatin analogs

      Study Objectives:

        1. To determine whether the addition of weekly pegvisomant administrations improves quality
           of life

        2. To determine whether the addition of weekly pegvisomant administrations improves insulin
           sensitivity

      Study Population: Acromegalic patients, who have normalized their serum IGF-I levels down to
      the upper 25 centiles of normality during long-term treatment with monthly injections of a
      long-acting somatostatin analogue Number of Subjects: 20

      Procedures:

        -  Patients on treatment with Sandostatin LAR (SL) 20 - 30 mg per months i.m. or patients
           on treatment with Lanreotide autosolution (LA) 90 - 120 mg deep s.c. will be enrolled.

        -  For 4 months, all subjects will also receive weekly s.c. injections of either placebo or
           a fixed dose of 40 mg pegvisomant

        -  After a 4 weeks wash-out period, patients will switch from either placebo to pegvisomant
           or from pegvisomant to placebo

        -  Before, and after 2 and 4 months of each treatment period, serum efficacy parameters and
           quality of life (AcroQol ™/ PASQ™) will be assessed.

        -  Before and after 4 months of each treatment period, pituitary tumor size and insulin
           sensitivity (HOMA/SIGMA model) will be assessed. Duration of study: 9 months

      Hypothesis:

      •We postulate that co-administration of the growth hormone receptor antagonist pegvisomant
      will improve QoL and insulin sensitivity
    

Detailed Description

      Introduction Both lanreotide (Somatulin Autosolution ™ (SL)) and octreotide (Sandostatin LAR
      ™ (LAR)) are equally effective in controlling disease activity in acromegalic subjects with a
      normalization of serum insulin-like growth factor-I (IGF-I) levels in roughly 65%. However,
      SL is injected as a deep intramuscular injection, while LA is injected as a deep subcutaneous
      injection. Physicians, involved in the treatment of acromegalic patients know that
      biochemical control of the disease in their patients not necessarily means that all those
      patients stop complaining. To address these issues, Sonino and co-workers studied with
      several symptom questionnaires the effects on quality of life (QoL) of SL. Together with a
      significant decrease in growth hormone (GH) and IGF-I, treatment with SL significantly
      improved psychological distress, well-being and social fears (1). In another study on the
      efficacy of the novel GH receptor antagonist pegvisomant to lower serum IGF-I concentrations
      a questionnaire evaluating five clinical signs and symptoms of acromegaly showed dose
      dependent significant differences from placebo (2). Recently, Webb and co-workers reported
      the successful development of a disease-specific questionnaire suitable to measure
      health-related quality of life in acromegaly (ACROQOL) (3).

      No clear biochemical parameter appears to be available that correlates well with disease
      activity related quality of life (4). At the same time, serum GH concentrations and serum
      total IGF-I levels, but not QoL, are used as parameters to determine dosing of Sandostatin
      LAR, or any of the available medical therapies for acromegaly (5-8).

      The growth hormone receptor antagonist pegvisomant as monotherapy once daily normalizes IGF-I
      in virtually all acromegalics (9;10), but pegvisomant monotherapy is also very costly.
      Recently, we reported the results of a 42-week dose-finding study on the efficacy of the
      combination of long-acting somatostatin analogues once monthly and pegvisomant once weekly in
      26 patients with active acromegaly. Pegvisomant dose was increased until IGF-I levels
      normalized or until a weekly dose of 80 mg was reached. IGF-I levels normalized in 25 (95 %)
      with a median weekly dose of 60 mg pegvisomant. There were no signs of pituitary tumor growth
      but mild elevations in liver enzymes were observed in 10 patients (38%) (11). One of the
      potential advantages of combining pegvisomant with somatostatin analogues is that pegvisomant
      monotherapy improves insulin sensitivity compared to somatostatin analogues (12;13), although
      it is unclear yet whether or not long-term pegvisomant administration would improve insulin
      sensitivity in normal subjects (13;14). Therefore, one might expect that pegvisomant
      monotherapy has beneficial effects on insulin sensitivity, compared to the combination of
      both pegvisomant and somatostatin analogues, as the latter ones decrease insulin sensitivity
      by several mechanisms (13;15).

      Conclusion:

        -  So-called biochemically well controlled acromegalic subjects with normal serum IGF-I
           concentrations frequently still have an impaired QoL.

        -  These subjects, when controlled by long-acting somatostatin analogs have impaired
           insulin sensitivity because of the pharmacological properties of these somatostatin
           analogs.

        -  We postulate that co-administration of the growth hormone receptor antagonist
           pegvisomant will improve QoL and insulin sensitivity

      Objectives:

        1. To determine whether the addition of weekly pegvisomant administrations improves quality
           of life

        2. To determine whether the addition of weekly pegvisomant administrations improves insulin
           sensitivity

      Description of procedures:

        -  Patients on treatment with Sandostatin LAR (SL) 20 - 30 mg per months i.m. or patients
           treated with Lanreotide autosolution (LA) 90 - 120 mg deep s.c. will be enrolled.

        -  For 4 months, and after randomization, all subjects will also receive weekly s.c.
           injections of either placebo or a fixed dose of 40 mg pegvisomant

        -  After a 4 weeks wash-out period, patients will switch from either placebo to pegvisomant
           or from pegvisomant to placebo

        -  Before, and after 2 and 4 months of each treatment period, serum efficacy parameters and
           quality of life (AcroQol ™ , general QoL questionaire and PASQ Signs and Symptoms) will
           be assessed.

        -  Before and after 4 months of each treatment period, pituitary tumor size and insulin
           sensitivity (HOMA/SIGMA model (16)) will be assessed.

      Subjects Twenty acromegalic subjects who are seen at regular intervals at our out-patient
      facilities will be asked to participate. All subjects will be seen at the Clinical Research
      Unit.

      Inclusion criteria:

        -  Active acromegaly.

        -  Serum total IGF-I levels must have been normalized during long-term treatment with
           long-acting somatostatin analogs

        -  Age between 18 and 80

      Exclusion criteria:

        -  Any contra-indication for the use of long-acting somatostatin analogs, as e.g. the use
           of anti-coagulants.

        -  Subjects with pituitary tumors that compress the optic chiasm

        -  Patients with insulin dependent diabetes

        -  Patients with cancer

        -  Patients with kidney- or liver function disturbances

        -  Fertile female patients that refuse to take contraceptives during the study

      Study procedures Visit 1; baseline (week 0; 1 day prior to next monthly injection of
      long-acting SRIF analog))

        -  Review inclusion and exclusion criteria

        -  Obtain written informed consent

        -  Conduct a medical history and physical examination; record vital signs.

        -  Blood sampling: fasting IGF-I, insulin, GH, glucose, HbA1c, liver functions, lipid
           profile, free fatty acids, pegvisomant levels, pregnancy test in females.

        -  QoL assessment (AcroQol™/PASQ ™)

        -  MRI (recent MRI of < 3 months is also acceptable)

        -  Injection of the usual SL or LA dose

        -  randomization

        -  Start of weekly injections of 40 mg pegvisomant or placebo (16 injections in total)

      Visit 2, 3 (week 8 and 16; one day prior of weekly study drug/placebo injection)

        -  Blood sampling: fasting IGF-I, insulin, GH, glucose, HbA1c, liver functions, lipid
           profile, free fatty acids, pegvisomant levels

        -  QoL assessment (AcroQol™/PASQ ™)

        -  After week 16, all patients have their 4 weeks wash-out period

        -  MRI

      Visit 4 (week 20; end of wash-out)

        -  Blood sampling: fasting IGF-I, insulin, GH, glucose, HbA1c, liver functions, lipid
           profile, free fatty acids, pegvisomant levels

        -  Return of study medication for drug accountability

        -  QoL assessment (AcroQol™/PASQ ™)

        -  Start of second co-treatment period with weekly s.c injections of either placebo or 40
           mg fixed-dose pegvisomant (16 weekly injections)

      Visit 5, 6 (week 28 and 36; one day prior of weekly study drug/placebo injection)

        -  Blood sampling: fasting IGF-I, insulin, GH, glucose, HbA1c, liver functions, lipid
           profile, free fatty acids, pegvisomant levels

        -  Return of study medication for drug accountability

        -  QoL assessment (AcroQol™/PASQ ™)

        -  MRI
    

Study Phase

Phase 4

Study Type

Interventional


Primary Outcome

To assess if the addition of pegvisomant weekly will improve Quality of life (QoL). QoL will be assessed by the PASQ and AcroQol questionnaires

Secondary Outcome

 If the addition of pegvisomant will improve metabolic parameters such as Insulin sensitivity, lipids, Glucose, IGF-I ect.

Condition

Quality of Life

Intervention

Pegvisomant

Study Arms / Comparison Groups

 pegvisomant-placebo
Description:  patients in this arm received(as addition)for the first 8 weeks Pegvisomant and the later for 8 weeks Placebo. This was divided by a 4 weeks wash-out period.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

20

Start Date

October 2006

Completion Date

July 2007

Primary Completion Date

July 2007

Eligibility Criteria

        Inclusion Criteria:

          -  Active acromegaly.

          -  Serum total IGF-I levels must have been normalized during long-term treatment with
             long-acting somatostatin analogs

          -  Age between 18 and 80

        Exclusion Criteria:

          -  Any contra-indication for the use of long-acting somatostatin analogs, as e.g. the use
             of anti-coagulants.

          -  Subjects with pituitary tumors that compress the optic chiasm

          -  Patients with insulin dependent diabetes

          -  Patients with cancer

          -  Patients with kidney- or liver function disturbances

          -  Fertile female patients that refuse to take contraceptives during the study
      

Gender

All

Ages

18 Years - 80 Years

Accepts Healthy Volunteers

No

Contacts

, , 



Administrative Informations


NCT ID

NCT00642720

Organization ID

*P05.1649L

Secondary IDs

*P05.1649L CCMO


Study Sponsor

Erasmus Medical Center


Study Sponsor

, , 


Verification Date

March 2008