Effects of SomatoKine (Iplex)Recombinant Human Insulin-like Growth Factor-1/Recombinant Human Insulin-like Growth Factor-binding Protein-3 (rhIGF-I/rhIGFBP-3) in Myotonic Dystrophy Type 1 (DM1)

NCT ID: NCT00233519

Last Updated: 2012-06-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-11-30
• Study Completion Date: 2008-05-31

Brief Summary

The aim of this study is to investigate the safety and feasibility of daily subcutaneous injections of recombinant IGF1 complexed with IGF binding protein 3 (SomatoKine-INSMED) as a treatment for muscle wasting and weakness in myotonic dystrophy type 1.

Conditions

Myotonic Dystrophy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1- Two Escalating Doses of Iplex

0.5 and 1.0 mg/kg/day

Group Type: EXPERIMENTAL

SomatoKine/IPLEX

Intervention Type: DRUG

Cohort 1: self-administered subcuteanous injections of 0.5 mg/kg/day of iPlex for 8 weeks, followed by 1.0 mg/kg/day of iPlex for 16 weeks.

Cohort 2: consecutive 8 week treatments of 0.5, 1.0, and 2.0 mg/kg/day of iPlex for a total of 24 weeks by self-administered subcuteanous injection.

Cohort 2 - Three Escalating Doses of Iplex

0.5, 1.0, and 2.0 mg/kg/day

Group Type: ACTIVE_COMPARATOR

SomatoKine/IPLEX

Intervention Type: DRUG

Cohort 1: self-administered subcuteanous injections of 0.5 mg/kg/day of iPlex for 8 weeks, followed by 1.0 mg/kg/day of iPlex for 16 weeks.

Cohort 2: consecutive 8 week treatments of 0.5, 1.0, and 2.0 mg/kg/day of iPlex for a total of 24 weeks by self-administered subcuteanous injection.

Interventions

SomatoKine/IPLEX

Cohort 1: self-administered subcuteanous injections of 0.5 mg/kg/day of iPlex for 8 weeks, followed by 1.0 mg/kg/day of iPlex for 16 weeks.

Cohort 2: consecutive 8 week treatments of 0.5, 1.0, and 2.0 mg/kg/day of iPlex for a total of 24 weeks by self-administered subcuteanous injection.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• A clinical diagnosis of DM-1 according to accepted clinical research criteria.23 The clinical research criteria require each of the following: (1) clinically evident myotonia; (2) muscle weakness in a characteristic distribution (distal predominant); and (3) similar findings in a first degree relative.
• Age 21 to 60 years (inclusive).
• Ability to walk 30 feet without assistance (cane and leg bracing is permitted).
• Weakness of sufficient severity to justify treatment and provide a reasonable opportunity to observe a therapeutic effect. At the eligibility evaluation, eligible patients must show both of the following:

1. muscle strength in a distal muscle group (ankle dorsiflexors or deep flexors of the fingers) which is less than or equal to grade 4 (Medical Research Council grade).

2. muscle strength in a proximal or mid-limb muscle group (flexors or extensors of the knee, elbow, shoulder, or hip) which is which is greater than or equal to 4- (Medical Research Council grade).

• For patients that are not within driving distance to Rochester, a local health care provider in their area must be able to complete their home visits.
• Competent, willing, and able to give informed consent.
• Able to self-administer study medication by subcutaneous injection or caregiver available to administer study medication.

Exclusion Criteria

• Congenital DM-1. Congenital disease constitutes ~10% of all cases of DM-1. Early in life, the weakness in individuals with congenital DM-1 derives from maldevelopment of skeletal muscle rather than muscle degeneration. Later in life, these individuals are also subject to the added effects of a wasting process similar to classical DM-1. However, it is difficult to determine which of these phenomena are mainly to blame for weakness in a particular patient. Furthermore, more than 75% of patients with congenital DM-1 have mental retardation.
• Prior treatment with glucocorticoids, anabolic steroids, testosterone, growth hormone, or IGF-I within 1 year of entry; or any investigational agent within 60 days of entry.
• Any history of malignancy except for surgically cured skin cancer or pilomatricoma (benign tumor of the hair follicle that is associated with DM-1).
• Women of childbearing potential who are not using effective birth control; women who are pregnant or lactating.
• Medical illness which would prevent assessment of muscle strength or function. This exclusion would include individuals with orthopedic, cardiac, or pulmonary disorders which preclude proper positioning on the myometry testing table, or restrict their ability to tolerate repeated maximum muscle contractions.
• Known allergy to tetracycline.
• Diaphragmatic weakness such that patients are unable to tolerate supine position, or swallowing impairment such that patients are unable to maintain nutrition without use of gastrostomy.
• Symptomatic liver or kidney disease, insulin requiring diabetes or type 2 diabetes requiring oral anti-diabetic agents.
• Untreated thyroid disease (hypo or hyperthyroidism)
• Major psychiatric illness (major depression, bipolar disorder, or schizophrenia) within twelve months of entry.
• History of non-compliance with other therapies.
• Drug or alcohol abuse within 12 months of enrollment.
• In men, evidence of a mass lesion on clinical examination by their primary care physician within twelve months prior to entry into the study (specifically prostate or testicular mass on clinical exam or other signs of mass lesion) or evidence of mass lesion on chest x-ray. In men 50 years of age or older, prostate specific antigen (PSA) elevation above normal.
• In women, evidence for mass lesion on clinical examination by their primary care physician or gynecologist (specifically breast & pelvic exam) within 12 months of entry into the study or evidence of mass lesion on chest x-ray. In women 40 years of age or older, evidence of mass lesion on mammogram. Women with Gail Scores > 1.7 will be excluded due to their increased risk of developing cancer.
• Atrial fibrillation/flutter; 2nd or 3rd degree heart block without pacemaker treatment
• Weight greater than 100 kilograms(kg).
• Body Mass Index greater than 30.
• History of bleeding diathesis or use of anticoagulant medications. Patients taking nonsteroidal anti-inflammatory agents will be asked to discontinue these medications 3 days prior to muscle biopsy.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Imsmed Incorporated

INDUSTRY

Sponsor Role: collaborator

University of Rochester

OTHER

Sponsor Role: lead

Responsible Party

Richard T Moxley

Professor of Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Richard T. Moxley, III, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Rochester

Locations

University of Rochester Medical Center

Rochester, New York, United States

Countries

United States

References

Heatwole CR, Eichinger KJ, Friedman DI, Hilbert JE, Jackson CE, Logigian EL, Martens WB, McDermott MP, Pandya SK, Quinn C, Smirnow AM, Thornton CA, Moxley RT 3rd. Open-label trial of recombinant human insulin-like growth factor 1/recombinant human insulin-like growth factor binding protein 3 in myotonic dystrophy type 1. Arch Neurol. 2011 Jan;68(1):37-44. doi: 10.1001/archneurol.2010.227. Epub 2010 Sep 13.

Reference Type: DERIVED

PMID: 20837825 (View on PubMed)

Related Links

http://www.dystrophyregistry.org

Webpage for the National Registry of Myotonic Dystrophy and Facioscapulohumeral Dystrophy patients and their family members.

Other Identifiers

5U54NS048843-03

Identifier Type: NIH

Identifier Source: secondary_id

View Link

5 U54 NS048843-03 A

Identifier Type: -

Identifier Source: org_study_id