Safety and Efficacy Study of Recombinant Human Insulin-Like Growth Factor-I/Recombinant Human Insulin-Like Growth Factor Binding Protein-3 (rhIGF-I/rhIGFBP-3) In Myotonic Dystrophy Type 1
- Conditions
- Myotonic Dystrophy Type 1
- Interventions
- Drug: placebo
- Registration Number
- NCT00577577
- Lead Sponsor
- Insmed Incorporated
- Brief Summary
To investigate the effects of rhIGF-I/rhIGFBP-3 treatment for 24 weeks on endurance, ambulation, cognitive functioning, insulin resistance, lipid levels, muscle function and strength, pain, gastrointestinal functioning, and quality of life endpoints in DM1 patients
- Detailed Description
Efficacy Measures:
Endurance, Ambulation, Cognitive function, Insulin resistance, Cholesterol and triglycerides, Muscle function and strength, Pain, Gastrointestinal function, Quality of life
MINIMUM INCLUSION CRITERIA
1. A diagnosis of DM1, confirmed by DM1 genetic mutation
2. Age 21 to 65 years (inclusive)
3. Ability to walk 30 feet - assistance with cane and/or leg bracing permitted
4. Able to self-administer study medication by subcutaneous injection or caregiver is available to administer study medication
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 69
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo placebo - rhIGF-I/rhIGFBP-3 rhIGF-I/rhIGFBP-3 -
- Primary Outcome Measures
Name Time Method Change From Baseline to Week 24 in Distance Walked as Assessed by the Six-minute Walk Test (6MWT) Distance Baseline and Week 24 The 6MWT measured the distance in meters that participants were able to walk over a total of six minutes. After a 10 minute resting period, the participants completed the 6MWT on a hard, flat surface at baseline and at Week 24.
Change From Baseline in Daily Step Count Baseline and Week 24 The number of steps taken per day was measured using a step activity monitor for 7 days at baseline and again at Week 24. Change from baseline scores were measured where a negative change from baseline indicates a decrease in the number of daily steps.
Peak Activity Index: Change From Baseline in Number of Steps Walked Per Minute During the 30 Minute Period of Fastest Walking Baseline and Week 24 The peak activity index measures the number of steps walked in the 30 minutes of fastest walking that occurred in a 24 hour period. This was measured using a step activity monitor for 7 days at baseline and again at Week 24. Change from baseline scores were measured where a positive change from baseline indicates an improvement in the number of steps walked during the 30 minute period of fastest walking.
Sustained Activity Index: Change From Baseline in the Highest Number of Steps Walked Per Minute Over 20 Minutes of Activity Baseline and Week 24 The sustained activity index measures the highest number of steps sustained over a continuous 20 minute period. This was measured using a step activity monitor for 7 days at baseline and again at Week 24. Change from baseline scores were measured where a positive change from baseline indicates an improvement in the number of steps walked over 20 minutes of activity.
Change From Baseline in Purdue Pegboard Test Scores Baseline and Week 24 The Purdue Pegboard Test consists of a board with two sets of 25 holes, 4 concave cups, and a number of small metal pins. Participants were required to pick up the pins from a holder and place them in the holes as quickly as possible over 30 seconds with their dominant hand. The score was calculated as the number of pins placed into holes in 30 seconds and was measured at baseline and Week 24. Change from baseline scores were measured where a positive change from baseline indicates an improvement in the number of pins placed in the board.
Change From Baseline in the Percentage of Time That Participants Spent Inactive Baseline and Week 24 Change from baseline scores were measured where a negative change from baseline indicates less time spent inactive.
Change From Baseline in Forced Vital Capacity (FVC) Volume While Sitting or Lying Down Baseline and Week 24 FVC is the volume of air that can be forcibly exhaled from the lungs after taking the deepest breath possible, as measured by spirometry.
Change From Baseline in Rey Complex Figure (RCF) Test Scores Baseline and Week 24 The Rey Complex Figure Test (RCFT) assesses visuospatial construction ability and visual memory through four different tests: copy (copying a complex geometric figure), immediate recall of the figure (drawing figure from memory at 3 minutes), delayed recall (drawing figure at 30 minutes after initial copy), and recognition score (selecting individual parts of the figure from sketches provided). Copy performances are divided into 18 components with a maximum score of 2 each. The maximum score for each figure is 36.
Change From Baseline in Letter-Number Sequencing (LNS) Test Scores Baseline and Week 24 The LNS test from the Welchsler Adult Intelligence Scale-III was used to assess working memory. The test required that participants recall, in order, numbers and letters presented in an unordered sequence. The number of items is 21. With each item being marked 0 if reported incorrectly or 1 if reported correctly, the maximum score is 21. Raw scores were converted into T-scores using available normative data. Change from baseline T-scores were measured where a positive change from baseline indicates improvement in performance.
Change From Baseline in Time Taken for Participants to Ascend and Descend 4 Stairs Baseline and Week 24 Participants were timed on their ability to climb up 4 stairs and timed separately to climb down 4 stairs at baseline and at week 24. The stairs were free-standing or the same flight of stairs was used at each assessment. Change from baseline scores were measured where a positive change from baseline indicates an improvement in the time taken for paticipants to ascend or descend 4 stairs.
Change From Baseline in Time Taken to Traverse 30 Feet Baseline and Week 24 Participants were timed on their ability to travel 30 feet on the same surface at each assessment at baseline and at Week 24. Change from baseline scores were measured where a positive change from baseline indicates an improvement in the time taken to travel 30 feet.
Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted While Sitting or Lying Down Baseline and Week 24 FVC is the volume of air that can be forcibly exhaled from the lungs after taking the deepest breath possible, as measured by spirometry.
Change From Baseline in Manual Muscle Test (MMT) Scores Baseline and Week 24 The MMT was used to assess muscle strength in the distal muscles and the proximal muscles. Distal muscles assessments included wrist extension, wrist flexion, ankle dorsiflexion and plantarflexion. Proximal muscle assessments included shoulder abduction, elbow extension, elbow flexion, hip extension, hip abduction, hip flexion, knee extension and knee flexion.
In MMT, each muscle assessment was given a score of 0 to 5, where 0 indicated 'no contraction palpable' and 5 indicated 'normal strength'. The scores from each muscle were summed and the maximum overall score of all measured muscles was 140, the maximum distal score was 40 and the maximum proximal score was 80. Higher scores indicated higher muscle strength. Change from baseline scores were measured where a positive change from baseline indicates an improvement in muscle strength.Change From Baseline in Selective Reminding Test T-Scores (Total Word and Delayed Words) Baseline and Week 24 The Selective Reminding Test measures verbal learning and memory and involves remembering a verbal list of 12 words. Participants were required to recall the 12 words presented. Words that were missed on recall were presented again, and the process was repeated until all 12 words were correctly recalled. The total word list recall and delayed recall were calculated as T-scores. Raw scores were converted to T-score using available normative data. Change from baseline T-scores were measured where a positive change from baseline indicates improvement in performance.
Change From Baseline in Selective Reminding Test Raw Scores (Cued Recall and Recognition) Baseline and Week 24 The Selective Reminding Test measures verbal learning and memory and involves remembering a verbal list of 12 words. Participants were required to recall the 12 words presented. Words that were missed on recall were presented again, and the process is repeated until all 12 words were correctly recalled. The cued recall scores ranged from 0-11 and multiple choice recognition scores ranged from 0-12. Change from baseline scores were measured where a positive change from baseline indicates an improvement in verbal recall and memory.
Change From Baseline in Trail Making Test (TMT) Scores Baseline and Week 24 The TMT assesses executive function, sequencing, mental flexibility, visual spanning speed and motor function. In TMT Part A, the participant had to draw lines in the correct order between 25 numbers randomly arranged on the page. In TMT Part B, the participant had to draw lines between 25 numbers and letters in alternating order (e.g., 1-A-2-B...etc). Times for Part A and Part B were used to derive T-scores which can range from a minimum of 0 and a maximum of 100. Raw scores were converted into T-scores using available normative data. Change from baseline T-scores were measured where a positive change from baseline indicates improvement in performance.
Change From Baseline in the Stroop Color Word Test Scores Baseline and Week 24 The Stroop Color Word Test measures selective attention and cognitive flexibility. The test has three parts, the Word test (reading words), the Color test (naming the ink color in which words are displayed) and the Color-Word test (saying the ink color not reading the word). An interference score was calculated from the Color, Word and Color-Word scores and is an indication of how well a person can complete a task while disregarding interfering information. Raw scores were converted into T-scores using available normative data. Scores range from 0 to 100. Change from baseline T-scores were measured where a positive change from baseline indicates improvement in performance.
Change From Baseline to Week 24 Scores on the Beck Depression Inventory II (BDI-II) Questionnaire Baseline and Week 24 BDI-II is a validated self-reported instrument of 21 questions which are each scored 0-3. Total scores range from 0-63, with higher score totals indicating more severe depression symptoms. {0-9: indicates minimal depression; 0-18: indicates mild depression; 19-29: indicates moderate depression; 30-63: indicates severe depression. Lower scores indicate no or minimal depression, with a maximum total score of 63.
Change From Baseline in Average Fasting Glucose Concentration in the Blood Baseline - Pre-dose and 30, 60, 90 and 120 minutes post glucose solution; Week 24 - Pre-dose and 30, 60, 90 and 120 minutes post glucose solution Participants were administered 75 grams (g) glucose solution prior to administration of the first dose of IPlex™ and after administration of the last dose. A 2-hour oral glucose tolerance test (OGTT) was performed under fasted conditions.
Change From Baseline in Average Fasting Insulin Concentration in the Blood Baseline - Pre-dose and 30, 60, 90 and 120 minutes post glucose solution; Week 24 - Pre-dose and 30, 60, 90 and 120 minutes post glucose solution Participants were administered 75 g glucose solution prior to administration of the first dose of IPLEX™ and after administration of the last dose. A 2-hour OGTT was performed under fasted conditions.
Change From Baseline in Qualitative Insulin Sensitivity Check Index (QUICKI) Baseline and Week 24 The QUICKI is based on fasting glucose and insulin measurements and are calculated using the following equation:
QUICKI = 1/\[ log(fasting glucose in mg/dL) + log (fasting insulin in uU/mL) \]Change From Baseline in Insulin Sensitivity Index-Matsuda (ISI-Matsuda) Baseline and Week 24 The ISI-Matsuda is based on the average glucose and insulin values obtained during the entire oral glucose tolerance test and are calculated using the following equation:
ISI = 10,000 / √ \[ fasting glucose (mg/dL) x fasting insulin(uU/mL) x mean glucose x mean insulin \]Change From Baseline in Total Blood Cholesterol Level Baseline and Week 24 A negative change from baseline indicates a decrease in total blood cholesterol level.
Change From Baseline in Total Blood Low-density Lipoproteins (LDL) Level Baseline and Week 24 A positive change from baseline indicates an increase in total blood LDL level.
Change From Baseline in Total Blood High-density Lipoproteins (HDL) Level Baseline and Week 24 A negative change from baseline indicates a decrease in total blood HDL level.
Change From Baseline in Total Blood Triglycerides Level Baseline and Week 24 A negative change from baseline indicates a decrease in total blood triglycerides level.
Change From Baseline in Gastro-esophageal Reflux Disease (GERD) Symptom Frequency Questionnaire (GSFQ) Scores Baseline and Week 24 The GSFQ contains 6 questions that assess the frequency of certain GERD symptoms and their impact on daily life. Scores were converted and reported out of 100 with higher scores indicative of more frequent and intense GERD symptoms. Change from baseline scores were measured where a negative change from baseline indicates less frequent and intense GERD symptoms.
Change From Baseline in Brief Pain Inventory (BPI) Questionnaire - Interference Scores Baseline and Week 24 The BPI contains 15 questions that assess the severity of pain and its impact or interference on functions of daily life. Pain interference is measured as the mean of 7 items on an 11-point scale where 0 indicates no interference and 10 indicates complete interference. A higher score indicates greater impairment due to pain. Change from baseline scores were measured where a positive change from baseline indicates a worsening of interference due to pain.
Change From Baseline in Gastrointestinal Symptom Rating Scale for Irritable Bowel Syndrome (GSRS-IBS) Questionnaire Scores Baseline and Week 24 The GSRS-IBS has 13 questions aimed at identifying the frequency and intensity of IBS symptoms during the past week. Answers are given a score from 1 (no discomfort at all) to 7 (very severe discomfort). A total score was calculated and ranged from 0 to 78. A lower score indicates less discomfort from IBS symptoms. Change from baseline scores were measured where a positive change from baseline indicates increased discomfort from IBS symptoms.
Change From Baseline in Swallowing Disturbance Questionnaire (SDQ) Scores Baseline and Week 24 The SDQ had 15 questions relating to the oral phase and pharyngeal phase of swallowing. Answers for 14 questions were assigned a number (0-3) based on a 4-point verbal scale (never, seldom, frequently, very frequently) and the last question was a yes or no question about respiratory infections. A higher score is indicative of greater swallowing issues with 44.5 as the highest possible score. A total score of ≥ 11 suggests impairment. Change from baseline scores were measured where a positive change from baseline indicates increased swallowing impairment.
Change From Baseline in Short Form (36) (SF-36) Questionnaire Scores Baseline and Week 24 The SF-36 is a 36-item questionnaire that evaluates quality of life through physical and mental health across eight scales, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability. Change from baseline scores were measured where a positive change from baseline indicates an improvement in quality of life.
Change From Baseline in Brief Pain Inventory (BPI) Questionnaire - Severity Scores Baseline and Week 24 The BPI contains 15 questions that assess the severity of pain and its impact or interference on functions of daily life. Pain severity was measured as the mean of 7 items of the questionnaire on an 11-point scale where 0 indicates no pain and 10 indicates the worst pain. A higher score indicates greater pain. Categories assessed include worst pain in 24 hours and average pain. Change from baseline scores were measured where a positive change from baseline indicates a worsening in pain.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (12)
University of Texas Health Science Center
🇺🇸San Antonio, Texas, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Ohio State University Medical Center
🇺🇸Columbus, Ohio, United States
Universit of Texas Medical Branch
🇺🇸Galveston, Texas, United States
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Washington University Medical School
🇺🇸Saint Louis, Missouri, United States
University of California Irvine Medical Center; MDA, ALS and Neuromuscular Center
🇺🇸Orange, California, United States
University of Rochester, Neuromuscular Disease Center
🇺🇸Rochester, New York, United States
University of California, Davis
🇺🇸Sacramento, California, United States
Oregan Health and Science University
🇺🇸Portland, Oregon, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States