Combination Risedronate - Parathyroid Hormone Trial in Male Osteoporosis
Condition: Osteoporosis
MeSH terms: Osteoporosis
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to develop new treatment options for osteoporosis in men. The
      Investigators will study two medications and three treatment regimens. First, risedronate
      (FDA approved) will be studied as monotherapy. Second, the investigators will study
      injectable parathyroid hormone (PTH 134, teriparatide; FDA approved), as a therapy for male
      osteoporosis. PTH, a naturally occurring hormone produced by the parathyroid glands, is one
      of the most important regulators of bone metabolism. The drug being studied in this protocol,
      teriparatide, is the first aminoterminal 34 amino acids of the native 84amino acid peptide.
      Teriparatide contains all of the classical biological activities of native PTH. In studies of
      postmenopausal women, in a small study of 23 men with osteoporosis and a larger study of 437
      men treatment with teriparatide led to significant increases in bone density. Although
      teriparatide and actonel are now approved for osteoporosis in men additional studies of these
      medications are needed in order to establish how best to use these drugs. This study is
      focused on an entirely new treatment approach, namely the combination of two medications for
      the treatment of osteoporosis risedronate with teriparatide to evaluate whether combination
      therapy is superior to therapy with either medication alone. This study is also designed to
      assess the extent to which risedronate maintains increases in bone density after a course of
      mono or combination therapy.
    

Detailed description: 
      Study Design:

      This study involves a 24month commitment, constituting 12 visits as outlined below. The study
      coordinator will contact patients remotely by phone or email at the Month 9 visit, the Month
      15, and the Month 21 visit so these do not require travel to Columbia University Medical
      Center.

      This randomized, doubleblind study has two phases. The first 18month phase has 3 arms.

      Patients will be randomized to receive either:

      Risedronate / arm 1; 33% of total number of patients Teriparatide / arm 2; 33% of total
      population or, The combination of Teriparatide and Risedronate / arm 3; 33% of total
      population.

      All patients will receive a daily subcutaneous injection with a small, 31 gauge needle
      (Teriparatide 20 ug or placebo vehicle), as well as a weekly pill (Risedronate 35 mg or
      placebo).

      The second phase of the study will last for 6 months. During this time, patients will stop
      their daily injections but will continue taking weekly pills. These pills will contain
      Risedronate for all patients.

      Thus, the second phase of the study, lasting 6 months, will have only one arm; that being,
      all participants will be on open label Risedronate for six months.

      TOTAL: 90 men

      Primary Endpoint: change in spine bone density in phase one of the study. The PRIMARY OUTCOME
      MEASURE in this study is the percentage change in lumbar spine bone density after 18 months
      of therapy comparing the three groups.

      Power analysis was conducted based upon ascertaining significance of change of the first 18
      months and the subsequent 6 months of the protocol. Based upon a 2-tailed test with an alpha
      of 0.05, the anticipated change in each of the three arms will be readily apparent at the
      lumbar spine with the "n" of 30 in each group.

      Secondary Endpoint: change in LS bone density at 24 months, change in hip and radius bone
      density in phase one and phase two of the study, change in bone markers, morphometric
      vertebral fractures at 18 months.

      VISIT ONE: Screening visit:

      At this visit study staff will review the Consent Form (patient and person obtaining consent
      sign the consent form) and inclusion/exclusion criteria. They will collect demographic
      information, medical history, treatment history for patient's osteoporosis, and prior
      medication history.

      Physical exam of the mouth, thyroid/neck, heart, lungs, abdomen, extremities, skin, mental
      status, sensory/motor status, lymph nodes, musculoskeletal, general appearance, height,
      weight, and blood pressure will be performed in order to identify any conditions which may
      exclude the potential participant from the study. This will be hereto forth referred to as
      "Physical Exam" Blood will be collected from the patient. A total of 2 tablespoons of blood
      by volume will be drawn from the patient to test for serum calcium, creatinine, parathyroid
      hormone, hepatic function, (Total Protein, Albumin, Globulin, A/G Ratio, Total Bilirubin,
      Direct Bilirubin, Alkaline Phosphatase, ALT, AST), and testosterone levels to determine the
      patient's eligibility for the study. Approximately 1.5 tablespoons of blood will be stored
      for research. The blood will be tested later for bone markers.

      Duration: approximately 3 hours

      VISIT TWO: Baseline/0 visit:

      On this day patients begin their medications. Patients will learn how to administer
      injections (Teriparatide) and take the study pill (Risedronate) and will receive their first
      6months worth of study supplies. The study drugs are managed by the Columbia University
      Research Pharmacy. The number of injection pens and the number of pills given to the patient
      will be recorded in case report forms. This will be hereto forth referred to as "Study Drug
      Supply/ ReSupply". In addition to the study drugs, the patients will be required to take a
      multivitamin with at least 400 IU of vitamin D and at least 500 mg of calcium each day. This
      is considered standard of care for people with osteoporosis. The patient will be asked if
      he/she experiences leg cramps, fatigue, depression, constipation, increased urination, back
      pain/kidney stones, local irritation/inflammation at the injection site or difficulty
      swallowing/esophageal ulcers, or dental problems such as the need to have a tooth pulled,
      implant placed or other dental procedure, nonhealing mouth sore. The patient can respond that
      these symptoms are absent, mild, moderate, or severe. This information is collected as a
      baseline for comparison to symptoms that may develop as a consequence of study medication
      usage.

      This will be hereto forth referred to as "Adverse Events". Patients are asked about any
      changes in supplementary or prescription medications since the last visit. Patients are asked
      about any changes in treatments for conditions old or new since the last visit. Patients are
      asked if any medical conditions or events have occurred or significantly changed since the
      last visit. All information will be recorded in case report forms. This will be hereto forth
      referred to as "New Conditions/Con Meds".

      Blood will be collected from the patient. A total of 2 tablespoons of blood by volume will be
      drawn from the patient. Approximately 0.5 tablespoons of blood will be used to test blood
      calcium and creatinine to monitor the safety of the patient. This will be hereto forth
      referred to as "Blood Calcium/Creatinine". Approximately 1.5 tablespoons of blood will be
      stored for research. The blood will be tested later for bone markers.

      This will be hereto forth referred to as "Blood Storage." Urine will be collected from the
      patient. Urine will be collected over a 24hour period and stored for research and tested
      later for Calcium and Creatinine levels. This will be hereto forth referred to as "24 Hour
      Urine" Additionally, a spot urine sample will be collected from the patient at the visit.
      This will be stored for research and tested later for urine NTX. This will be hereto forth
      referred to as "Urine Storage" Xrays of the lumbar and thoracic spine (Lumbar and Thoracic AP
      and Lateral images) will be done to establish baseline fracture presence. This will be hereto
      forth referred to as "XRay".

      Dual Xray Absorptiometry (DXA) will be performed to establish baseline bone density. This
      will be hereto forth referred to as "BMD" Duration: approximately 3 hours

      VISIT THREE: Week 1:

      Procedures that are repeated include Blood Calcium/Creatinine, Blood Storage, Urine Storage,
      24 Hour Urine, Adverse Events, and New Conditions/Con Meds Duration: approximately 30 minutes

      VISIT FOUR: Month 1:

      Procedures that are repeated include Blood Storage, Urine Storage, Adverse Events, and New
      Conditions/Con Meds Duration: approximately 30 minutes

      VISIT FIVE: Month 3:

      Procedures that are repeated include Blood Calcium/Creatinine, Urine Storage, Adverse Events,
      and New Conditions/ Con Meds Duration: approximately 30 minutes

      VISIT SIX: Month 6:

      Procedures that are repeated include Physical Exam, Study Drug Supply/ ReSupply, Blood
      Calcium/Creatinine, Blood Storage, Urine Storage, BMD, Adverse Events, and New Conditions/Con
      Meds Duration: approximately 1.5 hours.

      VISIT SEVEN: Month 9: phone visit:

      Procedures that are repeated include Adverse Events, and New Conditions/Con Meds.

      Duration: Approximately 15 minutes.

      VISIT EIGHT: Month 12:

      Procedures that are repeated include Study Drug Supply/ ReSupply, Blood Calcium/Creatinine,
      Blood Storage, Urine Storage, BMD, XRay, Adverse Events, and New Conditions/Con Meds
      Duration: approximately 2.5 hours.

      VISIST NINE: Month 15: phone visit:

      Procedures that are repeated include Adverse Events, and New Conditions/Con Meds Duration:
      Approximately 15 minutes.

      VISIT TEN: Month 18:

      Termination from phase 1 and entry into phase 2. Procedures that are repeated include
      Physical Exam, Blood Calcium/Creatinine, Blood Storage, Urine Storage, 24 Hour Urine, BMD,
      XRay, Adverse Events, and New Conditions/Con Meds. Study Drug Supply/ ReSupply will also
      occur. Of note, this will be Risedronate only, no more injectable medication). Patients
      therefore will only be given a supply of 6months worth of study pills.

      Duration: approximately 2.5 hours

      VISIT ELEVEN: Month 21: phone visit:

      Procedures that are repeated include Adverse Events, and New Conditions/Con Meds Duration:
      Approximately 15 minutes.

      VISIT TWELVE: Month 24: FINAL STUDY VISIT. Study physicians will discuss bone density results
      and recommend a course of poststudy treatment (if needed).

      Procedures that are repeated include Physical Exam, Blood Calcium/Creatinine, Blood Storage,
      Urine Storage, 24 Hour Urine, BMD, XRay, Adverse Events, and New Conditions/Con Meds.

      Termination from study occurs here. Duration: approximately 3.5 hours.
    

Intervention name(s): Risedronate; Teriparatide; Placebo Teriparatide; placebo Risedronate
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): weekly risedronate; daily teriparatide; daily placebo of teriparatide; weekly placebo of Risedronic Acid
Other intervention name(s): Actonel; Risedronic Acid; PTH1-34; Forteo; Teriparatide; PTH1-34; Forteo; Risedronate; Risedronic Acid
Intervention MeSH terms: Teriparatide; Risedronic Acid; Etidronic Acid; Parathyroid Hormone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: osteoporosis; male