4823
document
Efficacy and safety of recombinant human nerve growth factor in patients with diabetic polyneuropathy : A randomized controlled trial . rhNGF Clinical Investigator Group . CONTEXT Nerve growth factor is a neurotrophic factor that promotes the survival of small fiber sensory neurons and sympathetic neurons in the peripheral nervous system . Recombinant human nerve growth factor ( rhNGF ) has demonstrated efficacy as treatment for peripheral neuropathy in experimental models and phase 2 clinical trials . OBJECTIVE To evaluate the efficacy and safety of a 12-month regimen of rhNGF in patients with diabetic polyneuropathy . DESIGN Randomized , double-blind , placebo-controlled phase 3 trial conducted from July 1997 through May 1999 . SETTING Eighty-four outpatient centers throughout the United States . PATIENTS A total of 1019 men and women aged 18 to 74 years with either type 1 or type 2 diabetes and a sensory polyneuropathy attributable to diabetes . INTERVENTIONS Patients were randomly assigned to receive either rhNGF , 0.1 microg/kg ( n = 504 ) , or placebo ( n = 515 ) by subcutaneous injection 3 times per week for 48 weeks . Patients were assessed at baseline , 12 weeks , 24 weeks , and 48 weeks . MAIN OUTCOME MEASURES The primary outcome measure was a change in neuropathy between baseline and week 48 , demonstrated by the Neuropathy Impairment Score for the Lower Limbs , compared between the 2 groups . Secondary outcome measures included quantitative sensory tests using the CASE IV System , the Neuropathy Symptom and Change questionnaire , the Patient Benefit Questionnaire ( PBQ ) , and a global symptom assessment , as well as nerve conduction studies and occurrence of new plantar foot ulcers . Patients also were evaluated for presence of adverse events . RESULTS Among patients who received rhNGF , 418 ( 83 % ) completed the regimen compared with 461 ( 90 % ) who received placebo . Administration of rhNGF was safe , with few adverse events attributed to treatment apart from injection site pain/hyperalgesia and other pain syndromes . However , neither the primary end point ( P =.25 ) nor most of the secondary end points demonstrated a significant benefit of rhNGF . Exceptions were the global symptom assessment ( P =.03 ) and 2 of 32 comparisons within the PBQ , which showed a modest but significant benefit of rhNGF ( P =.05 for severity of pain in the legs and P =.003 for 6-month symptoms in the feet and legs ) . CONCLUSION Unlike previous phase 2 trials , this phase 3 clinical trial failed to demonstrate a significant beneficial effect of rhNGF on diabetic polyneuropathy . JAMA . 2000 ; 284:2215-2221 .
4824
Intervention_Physical
recombinant human nerve growth factor
4825
Intervention_Physical
Recombinant human nerve growth factor ( rhNGF )
4826
Intervention_Control
placebo-controlled
4827
Intervention_Pharmacological
rhNGF
4828
Intervention_Control
placebo
4829
Intervention_Physical
rhNGF
4830
Intervention_Control
placebo
4831
Intervention_Pharmacological
rhNGF
4832
Intervention_Pharmacological
rhNGF
4833
Intervention_Pharmacological
rhNGF
4834
Outcome_Other
Efficacy and safety
4835
Outcome_Other
efficacy and safety
4836
Outcome_Physical
change in neuropathy between baseline and week 48 , demonstrated by the Neuropathy Impairment Score
4837
Outcome_Physical
quantitative sensory tests using the CASE IV System , the Neuropathy Symptom and Change questionnaire , the Patient Benefit Questionnaire ( PBQ ) , and a global symptom assessment , as well as nerve conduction studies and occurrence of new plantar foot ulcers
4838
Outcome_Adverse-effects
adverse events .
4839
Outcome_Adverse-effects
adverse events
4840
Outcome_Pain
site pain/hyperalgesia and other pain syndromes
4841
Outcome_Physical
global symptom assessment
4842
Participant_Condition
diabetic polyneuropathy
4843
Participant_Condition
diabetic polyneuropathy
4844
Participant_Sample-size
1019
4845
Participant_Sex
men
4846
Participant_Sex
women
4847
Participant_Age
18 to 74
4848
Participant_Condition
type 1 or type 2 diabetes
4849
Participant_Condition
sensory polyneuropathy
4850
Participant_Condition
diabetes