High Protein and Exercise Therapy Plus Nocturnal Enteral Feeding in Juvenile-onset Pompe Disease

High Protein Nutrition and Exercise Therapy (HPET) Plus Nocturnal Enteral Feeding (NEF) in Juvenile-onset Pompe Disease.

The research protocol will be submitted for approval to the institutional review board of Columbia University Medical Center. An attempt will be made to recruit at least 6 juvenile patients between the ages of 8 and 17, preferably who are still ambulatory.

Subjects meeting all eligibility criteria will undergo a full history and physical examination, including details of age of onset of symptoms, distribution and severity of muscle weakness, muscle function, pulmonary function, and nutritional status. Subjects will undergo an electrocardiogram (ECG), spirometry, muscule strength evaluation, exercise capacity, functional muscle tests, laboratory tests, and muscle biopsy. Quality of life will be assessed via SF 36 questionnaire. Functional ability and level of handicap will be assessed by Rotterdam handicap scale. Written informed consent will be obtained from all subjects.

All patients, who will have received enzyme replacement therapy (ERT) for at least 2 years, will be evaluated prior to institution of high protein nutrition and exercise therapy plus nocturnal enteral feeding (HPET + NEF)(baseline), then again at 3 months, 6 months and 12 months into treatment. The following parameters will be evaluated-

• Skeletal Muscle Function
• Biochemical parameters from collected blood sample Muscle Biopsy will be obtained at baseline and at 12 months. Biopsy specimens, obtained from thigh muscle at baseline and a repeat biopsy of the corresponding area of the other leg at 12 months, will be analyzed as follows:.
• Histology and electron microscopy
• Autophagic and lysosomal function evaluation
• Body composition Body mass index (BMI), body composition, lean body mass, and fat mass will be measured at each visit by bioelectric impedance analysis using BI-101Q RJL Systems, software 3.1b

Study Overview

• Status: Withdrawn
• Conditions: Glycogen Storage Disease Type II
• Intervention / Treatment: Other: High Protein and Exercise Therapy along-with Nocturnal Enteral Feeding

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female, 8 to 17 years of age.
2. Diagnosis of Pompe disease; either by enzyme deficiency of muscle biopsy specimen or skin fibroblast culture, or homozygous or compound heterozygous for GAA mutation.
3. Muscle Function < grade 7 on Walton Scale.
4. Women of reproductive age (> 15 years) agree to use reliable methods of contraception during the study, if sexually active
5. Subject or legal representative is willing and able to provide written informed consent.

Exclusion Criteria:

1. Any intercurrent condition that may preclude accurate interpretation of study data
2. Obstructive pulmonary disease
3. Invasive ventilatory support
4. Noninvasive ventilatory support while awake and in an upright position
5. History of QTc prolongation > 450 msec for males and > 470 msec for females
6. Life expectancy < 1 year
7. History of allergy, sensitivity or any serious adverse reaction to rhGAA drug
8. Pregnancy
9. Current or recent drug or alcohol abuse.
10. Treatment with another investigational drug within 60 days of study start
11. Use of prohibited medication < 3 months prior to randomization
12. Otherwise unsuitable for the study in the opinion of investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: High Protein and Exercise therapy along-with Nocturnal Enteral	Other: High Protein and Exercise Therapy along-with Nocturnal Enteral Feeding; High Protein and Moderate Carbohydrate Nutrition designed by our nutritionist for every patient based on his/her nutrition requirements, age & gender; 500 cc Formula - Nutren Replete with Fiber overnight [8 hours] via gastrostomy tube; Conditioning Exercise once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in muscle function	Gross muscle function will be measured by the Walton Scale, the Timed Muscle Function Test and the Six-Minute Walk. Muscle strength will be measured by hand held dynamometer. Functional ability will be assessed by Rotterdam 9-item Handicap Scale.	Baseline, 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pulmonary function (Vital capacity, forced expiration volume)	The Pulmonary Function Test will be used to measure vital capacity (VC) and forced expiration volume (FEV1) to assess pulmonary function in sitting and supine positions.	Baseline, 12 months

Collaborators and Investigators

• Sponsor: Columbia University
• Investigators: Principal Investigator: Alfred E Slonim, MD, Columbia University

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: August 1, 2012
• First Submitted That Met QC Criteria: August 2, 2012
• First Posted (Estimate): August 3, 2012

Study Record Updates

• Last Update Posted (Estimate): April 13, 2015
• Last Update Submitted That Met QC Criteria: April 9, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Pompe disease; Acid Maltase Deficiency
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Lysosomal Storage Diseases, Nervous System; Glycogen Storage Disease Type II; Glycogen Storage Disease
• Other Study ID Numbers: AAAJ7305