A 48-Week (24-Week Baseline Followed by a 24-Week Treatment) Phase II Pilot Study of the Tolerability and Effect/Efficacy
of Subcutaneously Administered Insulin-Like Growth Factor-1 (rhIGF) (CEP-151) in Multiple Sclerosis (MS) Patients
This study has been completed.
Purpose
The drug rhIGF-1 (CEP-151) has been shown to play a key role preclinically in oligodendrocyte differentiation and survival,
as well as, myelin integrity and function. Moreover, in an animal model of MS, myelin expression, as well as that of its
receptors is upregulated at the time the myelin sheaths regenerate. Finally, administration of exogenous rhIGF-1 to rats
with EAE effectively, closes the disrupted BBB, reduces the number and severity of demyelinating lesions, and improves neurological
function. Thus it seems reasonable to examine the efficacy and safety, tolerability, and effect of CEP-151 on brain MRI lesions
in patients with MS.
Condition
|
Phase |
Multiple Sclerosis
|
Phase II
|
MedlinePlus related topics: Multiple Sclerosis
Study Type: Interventional
Study Design: Treatment, Safety/Efficacy
Further Study Details:
Expected Total Enrollment:
15
Study start: July 17, 1997;
Study completion: April 19, 2000
The drug rhIGF-1 (CEP-151) has been shown to play a key role preclinically in oligodendrocyte differentiation and survival,
as well as, myelin integrity and function. Moreover, in an animal model of MS, myelin expression, as well as that of its
receptors is upregulated at the time the myelin sheaths regenerate. Finally, administration of exogenous rhIGF-1 to rats
with EAE effectively, closes the disrupted BBB, reduces the number and severity of demyelinating lesions, and improves neurological
function. Thus it seems reasonable to examine the efficacy and safety, tolerability, and effect of CEP-151 on brain MRI lesions
in patients with MS.
Eligibility
Genders Eligible for Study:
Both
Patients must be between 18-55 years old; meet the diagnostic criteria for clinical definite or laboratory supported definite
MS with either a relapsing remitting or secondary progressive course;
Stage I - known by history to have a mean enhancing lesion frequency of 0.3 per month or greater;
Stage II - known by history to have a mean enhancing lesion frequency of 0.5 per month or greater;
Ability to comply with protocol requirements;
Provide written informed consent;
If a female patient, not of child bearing potential (surgically sterilized or post-menopausal) or if of child bearing potential,
documented to be nonpregnant by urine pregnancy test and not lactating with adequate contraception and counseling.
Male patients should also receive adequate counseling and exercise adequate contraception.
No clinically significant abnormalities on the prestudy laboratory evaluations, Physical examination, electrocardiogram (ECG),
chest x-ray, mammogram or opthalmologic exam.
No connective tissue or rheumatic disorder (systemic lupus erythematosus [SLE] ; rheumatoid arthritis [RA]; progressive systemic
sclerosis [PSS]; Sjogren's syndrome [SS]).
Patient may not be HIV (human immunodeficiency virus), HTLV-1 (human T cell leukemia virus), or HB/C Ag (hepatitis B or C
surface antigen) positive.
No history of insulin-producing tumors or reactive hypoglycemia.
No clinically significant medical condition (e.g., within 6 months of screen had myocardial infarction, angina pectoris, untreated
hypertension, and/or congestive heart failure [CHF] that, in the opinion of the investigator would compromise the safety of
the patient.
Ability to tolerate MRI examinations due to claustrophobia, or have contraindications to MRI scanning, such as pacemakers,
aneurysm clips, or shrapnel fragments. Welders and metal workers must have radiographic evidence to document lack of foreign
bodies in the eyes or they will be excluded, due to the risk of eye injury while in the MRI machine.
No history of substance use disorder (DSM-IV criteria) within the past two years.
No Type I or Type II diabetes treated with hypoglycemic agents (diet-controlled Type II diabetes may be included.)
No history of cancer (with the exception of localized skin cancers with no evidence of metastasis, significant invasion, or
recurrence) within three years of screening.
No first or second degree relatives with breast cancer.
Have not used an investigational drug within 30 days of the screen visit.
Have previously received interferon-alpha, interferon-beta, copolymer 1, cyclophosphamide, intravenous immunoglobulin, oral
myelin, or other immunosuppresive drugs within 6 months of screen.
Location
Information
Maryland National Institute of Neurological Disorders and Stroke (NINDS), 9000 Rockville Pike,
Bethesda,
Maryland,
20892,
United States
More Information
Publications
Liu X, Linnington C, Webster HD, Lassmann S, Yao DL, Hudson LD, Wekerle H, Kreutzberg GW. Insulin-like growth factor-I treatment
reduces immune cell responses in acute non-demyelinative experimental autoimmune encephalomyelitis. J Neurosci Res. 1997 Mar
1;47(5):531-8.
Miller DH, Albert PS, Barkhof F, Francis G, Frank JA, Hodgkinson S, Lublin FD, Paty DW, Reingold SC, Simon J. Guidelines
for the use of magnetic resonance techniques in monitoring the treatment of multiple sclerosis. US National MS Society Task
Force. Ann Neurol. 1996 Jan;39(1):6-16.
Stone LA, Frank JA, Albert PS, Bash C, Smith ME, Maloni H, McFarland HF. The effect of interferon-beta on blood-brain barrier
disruptions demonstrated by contrast-enhanced magnetic resonance imaging in relapsing-remitting multiple sclerosis. Ann Neurol.
1995 May;37(5):611-9.
Study ID Numbers:
970148; 97-N-0148
Record last reviewed:
April 21, 1999
Last Updated:
April 21, 1999
Record first received:
November 3, 1999
ClinicalTrials.gov Identifier:
NCT00001669Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-10-20