A Study to Characterise the Physiology of Weight Loss and Regain Under Dietary, Behavioural and Pharmacological Interventions in Healthy Obese Subjects

NCT01597609 | Completed Phase 1

• 1 other identifier: 110739
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Approximately 60 obese, but otherwise healthy, subjects will be assessed in this benchmark study to investigate the physiological changes associated with weight loss and regain. The aim is to estimate the changes in body composition during and after three interventions (i) calorie restricted diet + a marketed anti-obesity drug (sibutramine )(ii) calorie restricted diet + sibutramine placebo, and (iii) calorie restricted diet + moderate exercise. The interventions will last 12 weeks, after which there is a further 12 week observation period during which subjects will return to their normal lifestyle and are expected to regain weight. Additionally, a range of biomarkers may be evaluated to determine whether there are correlations at early and late time points with weight and fat loss and weight and fat regain. The changes in body composition and other biomarkers will be used to determine whether mathematical models can be built that predict the weight loss and regain of individual subjects. In addition, the usefulness of tools that may aid the physiological characterisation of weight loss/regain will be assessed, in particular methods for measuring energy expenditure and energy intake such as ambulatory activity meter, Sussex Ingestion Pattern Monitor ™ (SIPM), hunger-satiety VAS, indirect calorimetry and, if available, the Theranos in-home graphical user interface (GUI) portal. Knowledge of the body composition changes resulting from these typical weight loss interventions and predictive markers of response would facilitate the design of future studies for novel anti-obesity agents and allow earlier, more informed triaging of NCEs.

Conditions

Obesity

Outcome Measures

Primary Outcomes (3)

• Measures of body composition (fat mass, lean mass and total body water) using Echo MRI-AH and DEXA during the intervention and follow-up phases

  estimate the changes during and after three interventions: (i) calorie restricted diet + a marketed anti-obesity drug (sibutramine), (ii) calorie restricted diet + sibutramine placebo, and (iii) calorie restricted diet + moderate exercise + sibutramine placebo

  24 Weeks

• Measures of body weight and body mass index (BMI) during the intervention and follow-up phases.

  estimate the changes during and after three interventions: (i) calorie restricted diet + a marketed anti-obesity drug (sibutramine), (ii) calorie restricted diet + sibutramine placebo, and (iii) calorie restricted diet + moderate exercise + sibutramine placebo

  24 weeks

• Measures of waist and hip circumference during the intervention and follow-up phases.

  estimate the changes during and after three interventions: (i) calorie restricted diet + a marketed anti-obesity drug (sibutramine), (ii) calorie restricted diet + sibutramine placebo, and (iii) calorie restricted diet + moderate exercise + sibutramine placebo

  24 weeks

Secondary Outcomes (4)

• Mathematical models that use biomarkers of (i) body composition and metabolic status, (ii) macronutrient intake, and (iii) energy expenditure to predict later changes in weight and body composition during the intervention and follow-up phases.

  24 Weeks

• Measures of energy expenditure

  24 Weeks

• Measures of food intake, satiety and satiation

  24 Weeks

• Measures of insulin sensitivity

  24 Weeks

Study Arms (3)

Cohort A

EXPERIMENTAL

\- 600 Kcal deficit, Sibutramine placebo

Other: sibutramine placebo

Cohort B

EXPERIMENTAL

\- 600 Kcal deficit, Sibutramine 10 mg once daily

Drug: sibutramine

Cohort C

EXPERIMENTAL

\- 600 Kcal deficit, Moderate exercise (The energy expenditure will be equivalent to 30 minutes of brisk walking/5 times week i.e. \~1,000 Kcal/week) /sibutramine placebo

Other: sibutramine placebo

Interventions

sibutramine DRUG

10 mg, taken orally once per day for 12 weeks

Cohort B

sibutramine placebo OTHER

taken orally once per day for 12 weeks

Cohort A; Cohort C

Eligibility Criteria

• Age: 20 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject is a healthy male or female adult subject aged 20 to 55 years, inclusive.
• Subjects will be allowed in the study if they have medical conditions, such as asthma, which will not compromise the validity of the study in the opinion of the Principal Investigator and Medical Advisor.
• BMI within the range 30.0 to 40.0 kg/m2 inclusive.
• Has been obese from approximately the age of 18 or above.
• Has demonstrated previous weight loss sustained for a minimum of one month.
• Pre-menopausal female subjects of child bearing potential who are not pregnant or breast feeding will be eligible to participate if they comply with the following: Abstinence.
• The lifestyle of female subjects should be such that there is complete abstinence from intercourse from at least 30 days prior to receiving study medication and to continue until 30 days beyond the last study event, or 5 half lives of the study medication, whichever is the longest. If a subject claims abstinence as their method of contraception, they must agree to use a double barrier method (condoms, cervical/vault cap or diaphragm plus spermicide) should they become sexually active during the time frame described above. One of the following methods is acceptable as the sole method of contraception if there is indisputable data that it is \>99% effective, otherwise it should be used with a barrier method (condom or occlusive cap (diaphragm or cervical/vault caps) used with spermicidal foam/gel/film/cream/suppository): Documented tubal ligation, IUD or IUS, Oral contraception, Male partner sterilization (vasectomy) at least 6 months prior to the female subject's entry into the study and is the sole partner for that female subject. Condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository (Appendix 3).
• Subject has provided signed and dated, written informed consent prior to enrolment in the study.
• The subject is able to understand and comply with protocol requirements, instructions, and protocol-stated restrictions.

You may not qualify if:

• Has either a previous disease or current medical condition, which as judged by the Investigator, may affect the interpretation of data. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, haematological disease, neurological disease or endocrine disease.
• Currently has closed angle glaucoma.
• Has prostatic hypertrophy or hyperplasia.
• Females who are post-menopausal (post-menopausal females defined as being amenorrhoeic for more than 2 years with an appropriate clinical profile, e.g. history of vasomotor symptoms and confirmed by an FSH ≥ 40 mIU/mL).
• Known history of panic attacks and/or claustrophobia or other conditions precluding safe DEXA and Echo MRI-AH scans according to local guidelines, (e.g., pacemaker, hearing aid, metallic body piercing and/or other metal implants) or in the opinion of the Investigator the subject exceeds size limitations for the instruments.
• Has a history of clinically significant eating disorders (diagnosed and/or treated) such as previous anorexia nervosa, binge-eating disorder or bulimia nervosa.
• Has a recent history of weight loss (or gain) defined as a change of ≥ 5 % in the 3 months prior to screening.
• Has a history of being obese in childhood.
• Has had bariatric surgical intervention for obesity.
• Has a confirmed diagnosis of polycystic ovary syndrome.
• Has a history of alcohol or substance abuse or dependence in the 6 months prior to screening as determined by the Investigator. Abuse of alcohol, defined for males, as an average weekly intake of greater than 21 units (or an average daily intake of greater than 3 units), or defined for females, as an average weekly intake of greater than 14 units (or an average daily intake of greater than 2 units). One unit is equivalent to a half-pint (220mL) of beer or 1 (25mL) measure of spirits or 1 glass (125mL) of wine.
• Subjects will not be eligible if they plan to alter their current smoking (or other tobacco use) status during the course of the study, or if they have quit smoking less than 3 months prior to screening. Because of the effects of tobacco smoke on biomarkers, subjects may be classified as 'never smokers' or 'current smokers (abstaining at study visit) + former smokers'.
• Subjects who could not refrain from smoking during the time of the visit in the unit.
• Has a positive urine drug test at screening or pre-intervention. At a minimum, subjects will be screened for amphetamines, barbiturates, cocaine, opiates, cannabinoids, and benzodiazepines, and may be screened randomly throughout the study.
• Positive results for hepatitis C antibodies, hepatitis B surface antigen, or HIV at screening. If negative results have been obtained in the last 6 months, it is not necessary to repeat the tests unless indicated by clinical judgment.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Cambridge, Cambridgeshire, CB2 2GG, United Kingdom

Location

Related Links

• Results for study 110739 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Obesity

Interventions

sibutramine

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2012
• First Posted: May 14, 2012
• Study Start: May 22, 2008
• Primary Completion: March 4, 2010
• Study Completion: March 4, 2010
• Last Updated: June 20, 2017

Record last verified: 2017-06

Locations

GB (1)