Effect of GSP3 on Body Weight in Overweight and Obese Subjects (FLOW)

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Assessing the Effect of GSP3 on Body Weight in Overweight and Obese Subjects

The FLOW (First Loss Of Weight) study is designed to assess the effects of repeated administration of GSP3, an investigational product, on body weight. It is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study. FLOW is being conducted in 5 medical centers in Italy, Czech Republic, and Denmark, and will randomize 123 overweight and obese adult males and females to receive either placebo, GSP3 (2.25g), or GSP3 (3.75g) in addition to a hypocaloric diet (-600 kcal/day) for 12 weeks.

Study Overview

• Status: Completed
• Conditions: Obesity; Overweight
• Intervention / Treatment: Dietary supplement: Avicel (modified Cellulose); Device: GSP3

• Study Type: Interventional
• Enrollment (Actual): 128
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Czechia
  • Hradec, Czechia, 500 00
    • Hradec Kralove
  • Prague, Czechia, 121 08
    • Charles University
• Denmark
  • Copenhagen, Denmark, DK-1958
    • University of Cophenhagen
• Italy
  • Naples, Italy, 80131
    • Federico University Hospital
  • Rome, Italy, 00161
    • Policlinico Umberto I

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Body Mass Index (BMI) ≥ 27 and ≤ 35 (at least 30% overweight and 30% obese subjects)
2. Ability to follow verbal and written instructions
3. Informed Consent Form signed by the subjects

Exclusion Criteria:

1. Pregnancy or lactation
2. Absence of medically approved contraceptive methods in females of childbearing potential (e.g., hysterectomy, non-oral contraceptive medications or intrauterine device combined with a barrier method, two combined barrier methods such as diaphragm and condom or spermicide; bilateral tubal ligation and vasectomy are not acceptable contraceptive methods)
3. History of allergic reaction to carboxymethylcellulose, citric acid, modified cellulose, microcrystalline cellulose, and gelatin
4. Administration of investigational products within 1 month prior to Screening Visit
5. Night-shift workers
6. Subjects who stopped smoking within 6 months prior to Screening Visit or considering smoking cessation during the study
7. Subjects anticipating surgical intervention during the study
8. Known type 1 or type 2 diabetes
9. History of eating disorders including binge eating (except mild binge eater)
10. Weight change > 3 kg within 3 months prior to and during the Screening period
11. Supine systolic blood pressure (SBP) > 150 mm Hg and/or supine diastolic blood pressure (DBP) > 90 mm Hg
12. Angina, coronary bypass, or myocardial infarction within 6 months prior to Screening Visit
13. History of gastroesophageal reflux disease
14. History of gastric or duodenal ulcer
15. History of gastroparesis
16. History of gastric bypass or any other gastric surgery
17. History of intragastric balloon
18. History of pancreatitis
19. History of hemorrhoids
20. History of malabsorption
21. Laxative users
22. History of hepatitis B or C
23. History of human immunodeficiency virus
24. History of cancer within the past 5 years (except adequately-treated localized basal cell skin cancer or in situ uterine cervical cancer)
25. Any other clinically significant disease interfering with the assessments of Attiva, according to the Investigator
26. Positive serum or urine pregnancy test(s) in females of childbearing potential
27. Plasma glucose ≥ 126 mg/dL (7.0 mmol/L)
28. Abnormal serum thyrotropin (TSH)
29. Serum triglycerides > 500 mg/dL (5.65 mmol/L)
30. Positive test for drugs in the urine
31. Any relevant biochemical abnormality interfering with the assessments of Attiva, according to the Investigator
32. Anti-obesity medications (including herbal preparations) within 1 month prior to Screening Visit
33. Systemic corticosteroids within 1 month prior to Screening Visit
34. Thyroid hormones or preparations within 1 month prior to Screening Visit (except in subjects on stable dose of replacement therapy for at least 1 month)
35. Any other medication known to cause weight loss or weight gain within 1 month prior to Screening Visit
36. Medications treating hypertension within 1 month prior to Screening Visit
37. Medications treating dyslipidemia within 1 month prior to Screening Visit
38. Anticipated requirement for use of prohibited concomitant medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Microcyrstalline cellulose (Avicel): provided in 5 capsules (350 mg each), twice daily (BID) prior to lunch and dinner.	Dietary supplement: Avicel (modified Cellulose); Each capsule of Avicel contains approximately 350 mg of microcrystalline cellulose
Experimental: GSP3 (2.25g); GSP3: provided in 3 capsules (750 mg each), plus 2 placebo capsules (350 mg each), twice daily (BID) prior to lunch and dinner	Dietary supplement: Avicel (modified Cellulose); Each capsule of Avicel contains approximately 350 mg of microcrystalline cellulose; Device: GSP3; Each capsule of GSP3 (previously Attiva) contains 700 mg of a mixture of two food-grade materials: carboxymethylcellulose that is cross-linked with citric acid.
Experimental: GSP3 (3.75g); GSP3: provided in 5 capsules (750 mg each), twice daily (BID) prior to lunch and dinner	Device: GSP3; Each capsule of GSP3 (previously Attiva) contains 700 mg of a mixture of two food-grade materials: carboxymethylcellulose that is cross-linked with citric acid.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Body Weight	Change from baseline in kilograms and percent (%) weight	Measured at weeks 0,1,2,4,6,8,10,12,13, and follow up (week 14)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body weight responders	Change from baseline in body weight of at least 5%	12 weeks
Change in waist circumference	Change from baseline in waist circumference (centimeters)	Measured at weeks 0,1,2,4,6,8,10,12,13, and follow up (week 14)
Change in fat mass	Change in percentage (%) of total mas from baseline in fat- and bone-free fat mass measured by dual energy X-ray absorptiometry (DEXA)	Measured at weeks 0 and 13
Change in bone-free fat mass	Change in percentage (%) of total mas from baseline in fat- and bone-free fat mass measured by dual energy X-ray absorptiometry (DEXA)	Measured at weeks 0 and 13
Change in appetite (hunger, satiety, and fullness)	Assessed by self-administered Visual Analog Scale (VAS)	Measured at weeks 0,1,2,4,6,8,10,12,13, and follow up (week 14)
Change in food intake	Assessed by 24 hr dietary recall	Measured at weeks 0 and 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in plasma glucose	Change from baseline in millimoles per liter (mmol/L)	Measured at baseline and week 13
Change in plasma glucose status (normal, impaired, diabetic)		Measured at weeks 0 and 13
Change in serum insulin	Change from baseline in miliunits per liter (mU/L)	Measured at weeks 0 and 13
Change in insulin resistance	Change from baseline in homeostatic model assessment of insulin resistance (HOMA-IR)	Measured at weeks 0 and 13
Change in glycosylated hemoglobin (HbA1c)	Measured in percentage (%)	Measured at weeks 0 and 13
Change in total cholesterol, serum low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol/HDL ratio, and triglycerides	measured in mg/dL	Measured at weeks 0 and 13
Change vital signs: heart rate, supine and standing systolic and diastolic blood pressure (SBP, DBP)	Measured in beats per minute (heart rate) or millimeters of mercury (mmHg) for blood pressure	Measured at weeks 0,1,2,4,6,8,10,12,13, and follow up (week 14)
All adverse events (AE), serious adverse events (SAE), and gastrointestinal symptoms	Number and % of subjects with AE/SAEs spontaneously reported; gastrointestinal symptoms solicited via questionnaire	Measured at weeks 0,1,2,4,6,8,10,12,13, and follow up (week 14)
Change in serum sodium	Change from baseline in millimoles per liter (mmol/L)	Measured at weeks 0,4,8,12,13 and follow up (week 14)
Change in serum potassium	Change from baseline (mmol/L)	Measured at weeks 0,4,8,12,13 and follow up (week 14)
Change in serum coloride	Change from baseline (mmol/L)	Measured at weeks 0,4,8,12,13 and follow up (week 14)
Change in serum calcium	Change from baseline (mmol/L)	Measured at weeks 0,4,8,12,13 and follow up (week 14)
Change in serum magnesium	Change from baseline (mmol/L)	Measured at weeks 0,4,8,12,13 and follow up (week 14)
Change in serum phosphorus	Change from baseline (mmol/L)	Measured at weeks 0,4,8,12,13 and follow up (week 14)
Change in serum glucose	Change from baseline (mmol/L)	Measured at weeks 0,4,8,12,13 and follow up (week 14)
Change in blood urea nitrogen (BUN)	Change from baseline (mmol/L)	Measured at weeks 0,4,8,12,13 and follow up (week 14)
Change in serum creatinine	Change from baseline in micromoles per liter (umol/L)	Measured at weeks 0,4,8,12,13 and follow up (week 14)
Change in serum uric acid	Change from baseline (umol/L)	Measured at weeks 0,4,8,12,13 and follow up (week 14)
Change in total bilirubin	Change from baseline (umol/L)	Measured at weeks 0,4,8,12,13 and follow up (week 14)
Change in alanine aminotransferase (ALT)	Change from baseline in international units per liter (IU/L)	Measured at weeks 0,4,8,12,13 and follow up (week 14)
Change in aspartate transaminase (AST)	Change from baseline (IU/L)	Measured at weeks 0,4,8,12,13 and follow up (week 14)
Change in gamma-glutamyl transpeptidase (GGT)	Change from baseline (IU/L)	Measured at weeks 0,4,8,12,13 and follow up (week 14)
Change in alkaline phosphatase (ALP)	Change from baseline (IU/L)	Measured at weeks 0,4,8,12,13 and follow up (week 14)
Change in serum total protein	Change from baseline in grams per liter (g/L)	Measured at weeks 0,4,8,12,13 and follow up (week 14)
Change in serum albumin	Change from baseline (g/L)	Measured at weeks 0,4,8,12,13 and follow up (week 14)
Change in hematocrit	Change from baseline (%)	Measured at weeks 0,4,8,12,13 and follow-up (week 14)
Change in hemoglobin	Change from baseline (%)	Measured at weeks 0,4,8,12,13 and follow-up (week 14)

Collaborators and Investigators

• Sponsor: Gelesis, Inc.
• Investigators: Study Director: Hassan Heshmati, MD, Gelesis, Inc.

Publications and helpful links

General Publications

• Greenway FL, Aronne LJ, Raben A, Astrup A, Apovian CM, Hill JO, Kaplan LM, Fujioka K, Matejkova E, Svacina S, Luzi L, Gnessi L, Navas-Carretero S, Alfredo Martinez J, Still CD, Sannino A, Saponaro C, Demitri C, Urban LE, Leider H, Chiquette E, Ron ES, Zohar Y, Heshmati HM. A Randomized, Double-Blind, Placebo-Controlled Study of Gelesis100: A Novel Nonsystemic Oral Hydrogel for Weight Loss. Obesity (Silver Spring). 2019 Feb;27(2):205-216. doi: 10.1002/oby.22347. Epub 2018 Nov 13. Erratum In: Obesity (Silver Spring). 2019 Apr;27(4):679. Obesity (Silver Spring). 2019 Jul;27(7):1210.

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: December 19, 2016
• First Submitted That Met QC Criteria: December 30, 2016
• First Posted (Estimate): January 4, 2017

Study Record Updates

• Last Update Posted (Actual): May 15, 2018
• Last Update Submitted That Met QC Criteria: May 9, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: body composition; weight loss; satiety; glycemic control
• Additional Relevant MeSH Terms: Overweight; Body Weight
• Other Study ID Numbers: Attiva-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No